KR20060041179A - Hiv-1 envelope glycoproteins having unusual disulfide structure - Google Patents

Abstract

The present invention provides HIV- I envelope glycoproteins having unusual disulfide structure. In particular, the invention includes gpl 20 polypeptides, and polynucleotides encoding such polypeptides, as well as related vectors, host cells, and expression methods. The invention also encompasses immunogenic compositions containing gp120 polypeptides or polynucleotides and their use in eliciting a gp120-specific immune response. gp120 polypeptides and polynucleotides of the invention are also useful in diagnostic methods of the invention.

Description

HIV-1 envelope glycoprotein with abnormal disulfide structure {HIV-1 ENVELOPE GLYCOPROTEINS HAVING UNUSUAL DISULFIDE STRUCTURE}

The present invention relates generally to the field of immunogenic compositions useful for inducing or measuring immune responses against human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins gp120 and / or gp160. In particular, the present invention relates to immunogenic compositions comprising polypeptides comprising the gp120 sequence and / or polynucleotides (RNA or DNA) encoding such polypeptides, wherein such compositions comprise HIV-1 infection and / or disease (AIDS). Induces an immune response useful for the prevention or treatment of

Acquired immunodeficiency syndrome (AIDS) is caused by a retrovirus identified as human immunodeficiency virus (HIV). There has been considerable research to develop vaccines that induce a protective immune response based on the induction of antibodies or cellular responses. Recent studies have used subunit vaccines that use HIV proteins as immunogens in vaccines rather than attenuated or killed viruses for safety reasons. Subunit vaccines generally include gp120, which is part of an HIV envelope protein displayed on the surface of virion and virus infected cells. In this regard, gp120 mediates HIV-1 infection by free virion or cell-to-cell fusion. In both cases, gp120 initiates HIV-1 infection by binding to two cellular receptors, one receptor is CD4 and the other receptor is a chemokine receptor (typically CCR5 or CXCR4). Unique high affinity binding sites for the CD4 and chemokine receptors are located on the surface of the gp120 molecule.

HIV envelope proteins are well known and amino acid and nucleotide sequences for HIV envelopes from a number of HIV strains are known. The gp120 molecule consists of a 60,000 Dalton polypeptide core that is extensively modified by N-linked glycosylation to increase the apparent molecular weight of the molecule to 120,000 Daltons. The mature HIV-1 envelope proteins gp120 and gp41 are both derived from the common precursor gp160. The gp160 precursor contains an amino-terminal signal sequence that induces protein synthesis on membrane-bound ribosomes and ensures the translocation (secretory pathway) of the nascent polypeptide into the lumen of the endoplasmic reticulum. In the endoplasmic reticulum, the signal sequence is removed by signal peptidase, and the protein obtains a "simple" high-mannose type of N-linked carbohydrates by cotranslational action. The carbohydrate-containing protein is then transported to the Golgi apparatus, where many high-mannose carbohydrates are converted to "complex" sialic acid-containing carbohydrates. In addition, gp160 is converted to the gp120 / gp41 complex by proteolysis with purine or purine-like peptidase at the conserved glycoprotein processing site. The gp120 / gp41 complex then exits the cell surface, where it is believed to form a trimer structure. In cell membranes or virion membranes, gp120 exists as superficial membrane protein bound to gp41 by non-covalent interactions. In contrast, gp41 is an intrinsic membrane protein anchored in the membrane bilayer by a hydrophobic transmembrane domain located near the carboxyl terminus.

The amino acid sequence of gp120 contains five relatively conserved domains (C1-C5) interspersed with five hypervariable domains (V1-V5). The position of 18 cysteine residues in the gp120 sequence and the position of about 24 N-linked glycosylation sites in the gp120 sequence are conserved in most gp120 sequences. Hypervariable domains contain a wide range of amino acid substitutions, insertions and deletions. Sequence variations in these domains account for up to 30% overall sequence variability between gp120 molecules from various viral isolates. Despite this variation, all gp120 sequences retain the ability to interact with gp41 and bind to CD4 and chemokine (CCR5 and CXCR4) receptors to induce fusion of viral and host cell membranes.

Summary of the Invention

The present invention provides an immunogenic composition comprising an isolated polypeptide or isolated polynucleotide and a pharmaceutically acceptable carrier. The isolated polypeptide comprises a first gp120 amino acid sequence or an isolated polynucleotide encodes this first gp120 amino acid sequence, wherein the first gp120 sequence comprises at least the V2, V3, and C4 domains of gp120, and the HXB- of HIV gp120 Numbered from the N-terminal methionine of gp120 from two strains, (i) the first gp120 sequence was 54, 74, 119, 126, 131, 157, 196, 205, 218, 228 , At least one cysteine residue at one or more of positions 239, 247, 296, 331, 378, 385, 418 and 445, and / or (ii) the first gp120 sequence is 24, 29, 34, 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, 331, 378 At least one additional cysteine residue at positions other than 385, 418, 445, 493, 495, 499 to 501, 503 to 508 and 510. However, the first gp120 sequence is not a subtype G gp120 sequence with one or more additional cysteines in the V1 domain or a subtype E gp120 sequence with one or more additional cysteines in the V4 domain. In a preferred embodiment, the first gp120 sequence further comprises a V1 domain.

In one embodiment, the first gp120 sequence is selected from 54, 74, 119, 126, 157, 205, 218, 228, 239, 247, 331, 378, or 385. It lacks one or more cysteine residues in one or more positions.

In another embodiment, the first gp120 sequence is 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, One or more additional cysteine residues at positions other than 331, 378, 385, 418, or 445, provided that one or more additional cysteine residues are not present in the V1 domain of gp120.

The first gp120 sequence comprises a native gp120 sequence, preferably the gp120 sequence from the primary isolate of HIV. In a preferred embodiment, the first gp120 sequence comprises SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134 and 136 Each have at least about 99% identity with the V1, V2, V3, and C4 domains of gp120 selected from the group consisting of: In a more preferred embodiment, the first gp120 sequence has SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36 , 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86 , 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134 and 136 At least V1, V2, V3 and C4 domains of gp120 selected from the group consisting of:

In a preferred embodiment, the first gp120 sequence comprises odd cysteines. In a variation of this embodiment, the immunogenic composition comprises a polypeptide comprising a first gp120 sequence, wherein the cysteine in the first gp120 sequence is covalently linked to another polypeptide, preferably by disulfide bonds. The other polypeptide may comprise a second gp120 sequence. If the second gp120 sequence is identical to the first gp120 sequence, the first and second gp120 sequences form a homodimer. If the second gp120 sequence is different from the first gp120 sequence, the first and second gp120 sequences form a heterodimer. Other polypeptides may additionally or alternatively comprise gp41 amino acid sequences.

The present invention also provides an immunogenic composition comprising a polypeptide comprising a first gp120 sequence, wherein the cysteine in the gp120 sequence is cell-specific binding moiety, drug, immunostimulatory oligonucleotide (eg, CpG) And an agent selected from the group consisting of immunogenic carrier proteins.

In certain embodiments, an immunogenic composition comprises a polypeptide comprising a fusion polypeptide comprising a first gp120 sequence or a polynucleotide encoding such a fusion polypeptide.

The immunogenic composition may further comprise an adjuvant if desired.

The present invention also provides an isolated polypeptide comprising a first gp120 amino acid sequence, wherein the first gp120 sequence comprises at least the V2, V3 and C4 domains of gp120, and the N of gp120 from the HXB-2 strain of HIV gp120. Numbering from terminal methionine (a) the first gp120 sequence is 54, 74, 119, 126, 157, 205, 218, 228, 239, 247, 331, 378 or Lack one or more cysteine residues at one or more positions of 385, and / or (b) the first gp120 sequence is 54, 74, 119, 126, 131, 157, 196, 205, 218 At least one additional cysteine residue at a position other than 228, 239, 247, 296, 331, 378, 385, 418 or 445, provided that at least one additional cysteine residue Is not present in the V1 domain of gp120. However, the first gp120 sequence is not a subtype E gp120 sequence with one or more additional cysteines in the V4 domain. In a preferred embodiment, the first gp120 sequence further comprises a V1 domain.

In one embodiment, the isolated polypeptide is one of 54, 74, 119, 126, 157, 205, 218, 228, 239, 247, 331, 378 or 385. At least one position comprising a first gp120 sequence lacking at least one cysteine residue. In another embodiment, the isolated polypeptide is 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, 331 A first gp120 sequence comprising one or more additional cysteine residues at positions other than times 378, 385, 418, or 445, provided that one or more additional cysteine residues are not present in the V1 domain of gp120 Do not.

In a preferred embodiment, the isolated polypeptide is SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 , 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88 , 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134 and 136 A first gp120 amino acid sequence having at least about 99% identity with each of the V1, V2, V3, and C4 domains of gp120 selected from the group. In a more preferred embodiment, the first gp120 sequence has SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36 , 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86 , 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134 and 136 At least V1, V2, V3 and C4 domains of gp120 selected from the group consisting of:

In a preferred embodiment, the isolated polypeptide comprises a first gp120 sequence with an odd cysteine. In a variant of this embodiment, the cysteine in the first gp120 sequence is covalently linked with another polypeptide, preferably via disulfide bonds. The other polypeptide may comprise a second gp120 sequence. If the second gp120 sequence is identical to the first gp120 sequence, the first and second gp120 sequences form a homodimer. If the second gp120 sequence is different from the first gp120 sequence, the first and second gp120 sequences form a heterodimer. Other polypeptides may additionally or alternatively comprise gp41 amino acid sequences.

The invention also provides an isolated polypeptide wherein the cysteine in the gp120 sequence is covalently linked with an agent selected from the group consisting of cell-specific binding moieties, drugs, immunostimulatory oligonucleotides and immunogenic carrier proteins.

In certain embodiments, isolated polypeptides comprise fusion polypeptides comprising a first gp120 sequence. The fusion polypeptide may comprise a heterologous signal sequence, such as a herpes simplex virus glycoprotein D (gD-1) signal sequence or human tissue plasminogen activator signal sequence. The fusion polypeptide may additionally or alternatively comprise an epitope tag.

The invention also provides an isolated polynucleotide encoding any of the isolated polypeptides of the invention. When intended for use in the expression of an encoded polypeptide, the polynucleotide is preferably codon optimized for expression in a host cell of a particular species. In a preferred embodiment, the polynucleotides comprise SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, Group consisting of 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134 and 136 Encode a gp120 sequence having at least about 99% identity with each of the V1, V2, V3, and C4 domains of gp120 selected from. In a more preferred embodiment, the polynucleotide is SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 , 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87 , 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135 or these And a gp120 nucleotide sequence selected from the group consisting of subsequences of wherein the subsequences at least encode V1, V2, V3, and C4 of gp120.

Other aspects of the invention include vectors comprising any of the polynucleotides of the invention and host cells comprising such vectors. Preferred host cells include mammalian and bacterial cells.

The present invention also provides a method of preparing a polypeptide comprising the first gp120 amino acid sequence. In one embodiment, such methods comprise (a) introducing a vector of the invention into a cell and (b) expressing a polypeptide. The cells can be in vivo or in culture. When present in a culture, the method may further comprise recovering the polypeptide from the culture. In another embodiment, the polypeptide is prepared by (a) culturing a host cell of the invention comprising an expression vector under conditions suitable for expression of the polypeptide, and (b) recovering the polypeptide from the culture.

Another aspect of the invention is a method of immunizing an animal with a polypeptide comprising a first gp120 sequence. Such methods include administering an immunogenic composition of the invention to an animal.

The invention also determines whether a biological sample from a subject is contacted with (a) an isolated polypeptide comprising the gp120 amino acid sequence, and (b) the sample contains an antibody that specifically binds to the isolated polypeptide. It provides a diagnostic method comprising the. The gp120 sequence comprises at least the V2, V3 and C4 domains of gp120 and is numbered from the N-terminal methionine of gp120 from the HXB-2 strain of HIV gp120 (i) 54, 74, 119, 126, 131 At least one cysteine residue at one or more of 157, 196, 205, 218, 228, 239, 247, 296, 331, 378, 385, 418 and 445 Or / or (ii) 24, 29, 34, 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, One or more additional cysteines at positions other than 247, 296, 331, 378, 385, 418, 445, 493, 495, 499 to 501, 503 to 508 and 510 It includes residues. However, the gp120 sequence is not a subtype G gp120 sequence with one or more additional cysteines in the V1 domain or a subtype E gp120 sequence with one or more additional cysteines in the V4 domain. In a preferred embodiment, the gp120 sequence further comprises a V1 domain.

In another embodiment, the present invention provides a method for determining whether a biological sample from a subject comprises a polypeptide comprising a gp120 amino acid sequence having an abnormal cysteine number or a polynucleotide encoding such a gp120 amino acid sequence. It provides a diagnostic method comprising assaying a biological sample of. More specifically, the samples were numbered from the N-terminal methionine of gp120 from the HXB-2 strain of HIV gp120 (a) 54, 74, 119, 126, 131, 157, 196, 205 Lack one or more cysteine residues at one or more of positions 218, 228, 239, 247, 296, 331, 378, 385, 418 and 445, and / or (b) 24 , 29, 34, 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, 331, For a gp120 amino acid sequence comprising one or more additional cysteine residues at positions other than 378, 385, 418, 445, 493, 495, 499 to 501, 503 to 508 and 510 Is tested. Preferably, the gp120 sequence is not a subtype G gp120 sequence with one or more additional cysteines in the V1 domain or a subtype E gp120 sequence with one or more additional cysteines in the V4 domain.

In one variation of this embodiment, the assay is an immunoassay comprising contacting a sample with an antibody that specifically binds to the gp120 sequence under conditions suitable for binding.

In another variation of this embodiment, the assay is a polynucleotide based assay wherein the sample polynucleotide is contacted with a nucleic acid sequence that specifically hybridizes to a nucleotide sequence that encodes a gp120 sequence under conditions suitable for hybridization. In a preferred embodiment, the nucleic acid molecule can be one of a pair of amplification primers, in which case the assay contacts the sample polynucleotide with both amplification primers under conditions suitable for amplification, and then whether the amplification product is produced. Is determined by determining In another preferred embodiment, the nucleic acid molecule is a nucleic acid probe attached to a solid phase and the assay is performed by determining whether the sample polynucleotide is specifically hybridized to the nucleic acid probe.

The attached figure shows a schematic of the HIV-1 gp120 amino acid sequence. In all figures, the numbering for each amino acid residue position is based on the HIV-1 strain HXB2. Lines represent actual amino acid residues that are mutated, and amino acid residues are named using standard single molecule abbreviations. All variants are represented in the following format to indicate a substitution from one residue to another: Z to X-> Y (of HXB2), where X is the amino acid that is substituted, and Y is the substituted (ie new) amino acid. to be. Five variable regions and five conserved regions are shown as V1-V5 and C1-C5, respectively.

1 depicts positions 54 and 126 with substitutions where the Cys residue is changed to an Arg residue in sample U-101c1. The total cysteine complement is 16 residues.

FIG. 2 shows positions 131 and 228 with substitutions in which the Cys residue is changed to Arg and Tyr in sample U-178c13, respectively. Total cysteine complement is 16 residues.

3 shows an HIV-1 sample with total cysteine complement of 17 residues. The sample name is shown in parentheses after each variation.

4 shows an HIV-1 sample with total cysteine complement of 19 residues. Sample names are shown in parentheses after each variation.

5A-5X show HIV-1 samples with total cysteine complement of 20 residues. Sample names are shown below each figure. In this composite drawing, only regions with additional Cys residues are shown. In panels A through S, the number of residues in the loop (except Cys residues) is shown in the lower right of the panel. Panel T, showing U-374c1 and U-234c10, shows a set of potential secondary structures based on additional cysteines. Panel U shows various conformations for U-374c1 and U-208_4cl based on unique Cys pairings. Additional Cys residues in V2 (U-033c1) (Panel V), V4 (U-210c2) (Panel W), and V5 (U-062_2c5) (Panel X) are also shown.

The present invention provides an isolated polypeptide comprising a sequence from HIV gp120. This gp120 sequence has an abnormal disulfide structure. Specifically, the gp120 sequence of the present invention contains more or fewer cysteine residues than normal 18 cysteine residues. The gp120 sequences described herein were obtained in large scale clinical trials of HIV vaccines conducted at 61 clinical laboratories throughout North America, Puerto Rico and the Netherlands. During this course of study, gp120 encoding cDNA was cloned and sequenced from 350 recent HIV new infections. In this study, plasma samples were taken within 6 months of infection, plasma viral RNA was reverse transcribed, amplified by polymerase chain reaction (PCR) and sequenced. Surprisingly, about 20% of the obtained gp120 sequence had an abnormal disulfide structure. Thus, these structural features are found in a significant number of successful viruses early in the day before extensive variation can occur in the host. Thus, viruses with abnormal disulfide structures may represent the "transmission phenotype" associated with new infections or the major new variant of HIV-1 prevalent in North America. In either case, vaccines designed to prevent HIV-1 infection should be directed against viruses containing gp120 with abnormal disulfide structures.

Natural proteins containing an odd number of cysteines are abnormal because free sulfhydryl groups are highly reactive with other free sulfhydryl groups and tend to form intramolecular and intermolecular disulfide bonds. Of interest are the gp120 sequences of the invention, which contain an odd number of cysteines, which are used by the virus to create unpaired cysteine residues that can form extra intermolecular and intramolecular disulfide bonds and generate molecular diversity. It may represent a mechanism that is not known in the art. In principle, this diversity mediates covalent bonds between two gp120 molecules (each with unpaired cysteines), covalent bonds with cysteine residues in gp41, or covalent with another viral or cellular protein. It can occur by changing the intramolecular or intermolecular disulfide structure by mediating the bond.

Moreover, vaccine developers have developed HIV-1 envelope proteins containing unpaired cysteine residues to generate new antigens that more accurately replicate the structure of the gp120 / gp41 complex present on the surface of virion and virus infected cells. Can be used. For example, viral spikes present on the surface of HIV-1 virions and virus infected cells are believed to be non-covalent oligomers (typically trimers) of the monomeric gp120 / gp41 complex. Since these complexes are brittle and degrade, it was not possible to purify the monomer or oligomeric gp120 / gp41 complexes. However, it is believed that good HIV-1 vaccines can be developed if methods for preparing oligomeric gp120 / gp41 complexes can be developed. Indeed, some researchers have used in vitro mutagenesis to engineer unpaired cysteine residues into the structures of gp120 and gp41 to produce stable and covalently linked gp120 / gp41 complexes. Although covalently bound complexes are obtained, the resulting structures are not native structures and thus did not accurately replicate the structure of the gp120 / gp41 complexes such as those present in virion or virus infected cells. Many of the molecules described herein are naturally present and have cysteines that do not pair in defined regions far from those used conventionally for the production of disulfide stabilized gp120 / gp41 complexes. It offers a special opportunity for genetic engineering of various disulfide bound structures to enhance the immunogenicity of gp120. Exemplary structures include homodimers, gp120 / gp41 heterodimers, gp120 covalently linked to other HIV-1 proteins, gp120 linked to non-HIV-1 proteins, or gp120 covalently bound to non-protein chemical compositions. This structure can enhance immunogenicity beyond the immunogenicity achievable with monomers. The heterodimeric gp120 complex is useful for expanding the breadth of the immune response. For example, heterodimers containing gp120 sequences from two different HIV-1 subtypes can be used to induce an immune response against each HIV-1 subtype. In other embodiments, the gp120 sequence containing the free sulfhydryl group can be used, for example, to target (eg, enhance) immunogenicity or to target the gp120 sequence to a particular cell type (eg, dendritic cells or macrophages). by binding the gp120 sequence to a highly immunogenic carrier protein such as diphtheria toxin, keyhole limpet hemocyanin, tyroglobulin or bovine serum albumin). Since gp120 binds to cell surface antigen CD4 with high affinity, gp120 sequences containing free sulfhydryl groups can be bound to the drug for targeting to CD4-containing cells.

Justice

The terminology used herein is defined as set forth below unless otherwise noted.

The full length gp120 amino acid sequence is said to have one or more "additional cysteines" when the sequence contains more than 18 cysteine residues present in most full length gp120 sequences. In addition, a gp120 fragment has a "additional cysteine" if the full-length gp120 sequence from which it contains contains more cysteine residues than normal 18 cysteine residues and one or more of the extra cysteine (s) is present in the fragment. It is mentioned.

The term "immunogenic composition" means any composition capable of inducing an immune response.

As used herein, the term "vaccine" refers to an immunogenic composition ("prevention vaccine") that reduces the risk of or prevents infection by an infectious agent or an immunogenic composition that improves to any extent an existing infection (" Therapeutic vaccine "). If the vaccine protects the organism from subsequent attack by the infectious agent, such vaccine is referred to as "defense".

As used herein, the term "DNA vaccine" refers to a vaccine containing one or more polynucleotides encoding an antigen, wherein when such polynucleotides are administered to an organism, the immune response to these antigens is expressed after the encoded antigen is expressed. Happens.

The term "virus derived vaccine" as used herein refers to a virus containing a virus particle, a virus like particle (VLP), a virus particle or a virus infected cell displaying an antigen on a portion and / or surface of the VLP, such a particle. Or when cells are administered to an organism, an immune response against the displayed antigen is induced. The term "virus derived vaccine" includes chimeric virus particles or VLPs containing components from two or more different sources.

The terms "polypeptide" and "protein" are used interchangeably to mean polymers of amino acids and include atypical amino acids that can function in a similar manner to natural amino acids unless otherwise specified.

The term "isolated" as used in the context of a polypeptide or polynucleotide means a polypeptide or polynucleotide that is separated from one or more other components typically present with the polypeptide or polynucleotide. Thus, a natural polypeptide is isolated when it is purified from one or more other components that exist naturally with such polypeptide or polynucleotide. A recombinant polypeptide or polynucleotide is isolated when it is purified from one or more other components present when such polypeptide or polynucleotide is produced.

The term "amino acid" or "amino acid residue" includes natural L-amino acids or residues unless otherwise indicated. One- and three-letter abbreviations for commonly used amino acids are used herein (Lehninger, A. L. (1975) Biochemistry, 2d ed., Pp. 71-92, Worth Publishers, N. Y.). The terms "amino acid" and "amino acid residue" refer to D-amino acids as well as chemically modified amino acids, such as amino acid analogs, natural amino acids not normally incorporated into proteins, and chemically synthesized compounds having the characteristic properties of amino acids ( Collectively, “atypical” amino acids). For example, analogs or mimetics of phenylalamine or proline that allow conformational restriction of the same peptide compound as native Phe or Pro are included in the definition of “amino acid”.

Exemplary atypical amino acids include, for example, 2-amino adipic acid (Aad) which may be substituted for the amino acids described in International Publication No. WO 90/01940 as well as Glu and Asp; 2-aminopimelic acid (Apm) for Glu and Asp; 2-aminobutyric acid (Abu) for Met, Leu and other aliphatic amino acids; 2-aminoheptanoic acid (Ahe) for Met, Leu and other aliphatic amino acids; 2-aminoisobutyric acid (Aib) for Gly; Cyclohexylalanine (Cha) for Val, Leu and Ile; Homoarginine (Har) for Arg and Lys; 2,3-diaminopropionic acid (Dpr) for Lys, Arg and His; N-ethylglycine (EtGly) for Gly, Pro and Ala; N-ethylasparagine (EtAsn) for Asn and Gln; Hydroxylicin (Hyl) for Lys; Allohydroxylysine (Ahyl) for Lys; 3- (and 4-) hydroxyproline (3Hyp, 4Hyp) for Pro, Ser and Thr; Allo-isoleucine (Aile) for Ile, Leu and Val; N-methylglycine (MeGly, Sarcosine) for Gly, Pro and Ala; N-methylisoleucine (MeIle) for Ile; Norvaline (Nva) for Met and other aliphatic amino acids; Norleucine (Nle) for Met and other aliphatic amino acids; Ornithine (Orn) for Lys, Arg and His; Citrulline (Cit) and methionine sulfoxide (MSO) for Thr, Asn and Gln; N-methylphenylalanine (MePhe), trimethylphenylalanine, halo (F, Cl, Br and I) phenylalanine and trifluorylphenylalanine for Phe.

As used herein, the term "full length" refers to a polypeptide having the same length as a mature wild type polypeptide.

The term "fragment" as used with respect to a polypeptide or polynucleotide refers to a part of a macromolecule. Thus, polypeptide fragments lack the N-terminal portion, C-terminal portion, or both of the macromolecules. Polypeptide fragments are also referred to herein as "peptides". Fragments of polynucleotides may lack the 5 'portion, 3' portion or both of the macromolecules. Polynucleotide fragments are also referred to herein as "oligonucleotides". Oligonucleotides are relatively short nucleic acid molecules, generally shorter than 200 nucleotides, more particularly shorter than 100 nucleotides, most particularly shorter than 50 nucleotides. Typically, oligonucleotides are single stranded DNA molecules.

The "subsequence" of an amino acid or nucleotide sequence is part of a large sequence.

The terms "identical" or "percent identity" associated with two or more amino acid or nucleotide sequences are the same or the same when compared and aligned for maximal identity, as determined by visual inspection or using one of the following sequence comparison algorithms. By two or more sequences or subsequences having a specific proportion of amino acid residues or nucleotides.

For sequence comparison, typically one sequence functions as a reference sequence to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into the computer, subsequence coordinates are designated if necessary, and sequence algorithm program parameters are specified. The sequence comparison algorithm then calculates the percent sequence identity of the test sequence (s) relative to the reference sequence based on the designated program parameters.

The optimal alignment of the sequences for comparison is, for example, by Smith & Waterman's local homology algorithm (Adv. Appl. Math. 2: 482 (1981)). A search for similarity methods of Pearson & Lipman (Wunsch's homology alignment algorithm (J. Mol. Biol. 48: 443 (1970)) ((1988) Proc. Natl. By Acad. Sci. USA 85: 2444) by computerized implementation of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetic Computer Group, 575 Science Dr., Madison, WI). Or visual inspection (see Ausubel et al., Supra).

One example of a useful algorithm is PILEUP. PILEUP generates multiple sequence alignments from groups of related sequences using progressive pairwise alignments to indicate percent relationship and sequence identity. It also plots a tree or dendrogram showing the clustering relationships used to generate the alignment. PILEUP takes advantage of the simplification of Feng & Doolittle's progressive alignment method ((1987) J. Mol. Evol. 35: 351-360). The method used is similar to the method described by Higgins & Sharp ((1989) CABIOS 5: 151-153). The program can align up to 300 sequences, each with a maximum length of 5,000 nucleotides or amino acids. The multiple alignment procedure begins with a pair alignment of the two most similar sequences, resulting in a cluster of two aligned sequences. This cluster is then aligned with respect to the next most relevant sequence or cluster of aligned sequences. Two clusters of sequences are aligned by simple extension of the pair alignment of two individual sequences. Final alignment is achieved by a series of progressive pair alignments. The program is run by specifying their amino acid or nucleotide coordinates for a particular sequence and region of sequence comparison and by specifying program parameters. For example, reference sequences can be compared with other test sequences to determine percent sequence identity relationships using the following parameters: default gap weight (3.00), default gap length weight (0.10) and weighed terminal gap.

Another example of a suitable algorithm for measuring percent sequence identity and percent sequence similarity is the BLAST algorithm (Basic Local Alignment Search Tool (1990) J. Mol. Biol. 215: 403-410) described by Altschul et al. )to be. Software for performing BLAST analyzes is publicly available through the National Biotechnology Information Center (http://www.ncbi.nlm.nih.gov/). This algorithm is first determined by identifying short words of length W in the query sequence that match or satisfy the marginal score T of some positive values when aligned with words of equal length in the database sequence. Identifying a scoring sequence pair (HSP). T is referred to as the neighboring word score limit (Altschul et al, supra). This initial neighboring word hit acts as a seed in initiating a search to find longer HSPs containing them. The word hits are then stretched in both directions along each sequence as long as the cumulative alignment score can be increased. Cumulative scores are calculated using parameters M (compensation score for a pair of matching residues; always greater than 0) and N (penalty score for mismatching residues; always less than 0) for the nucleotide sequence. For amino acid sequences, a scoring matrix is used to calculate the cumulative score. The elongation of the word hit in each direction is such that the cumulative alignment score is reduced by an amount X from its maximum obtained value; The cumulative score is less than or equal to zero due to the accumulation of one or more negative-scoring residue alignments; It stops when it reaches the end of either sequence. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses a comparison of 11 strands of word length (W), 10 expected values (E), M = 5, N = -4, and both strands by default. For amino acid sequences, the BLASTP program uses, by default, a word length of 3 (W), an expected value of 10 (E), and a BLOSUM62 scoring matrix (see Henikoff & Henikoff (1989) Proc. Natl. Acad. Sci. USA 89: 10915).

In addition to calculating percent sequence identity, the BLAST algorithm also performs statistical analysis of the similarity between the two sequences (Karlin & Altschul 1993) Proc. Natl. Acad. Sci. USA, 90: 5873-5787). One measure of similarity provided by the BLAST algorithm is the minimum sum probability (P (N)), which provides an indication of the probability that a match between two nucleotide or amino acid sequences will occur by chance. For example, a nucleic acid is considered analogous to a reference sequence when the minimum sum probability is less than about 0.1, more preferably less than about 0.01, and most preferably less than about 0.001 in comparison of the test nucleic acid to the reference nucleic acid.

Residues in two or more polypeptides are said to be "correspond" when they are homologous (ie, occupy similar positions in the primary, secondary, or tertiary structure) or similar (ie, have the same or similar functional capacity). Is mentioned. As is well known in the art, homologous residues can be determined by aligning the polypeptide sequence for the maximum match described above.

The position in the gp120 amino acid sequence described herein is identified by position number, where the number is numbered from the N-terminal methionine of gp120 (SEQ ID NO: 138) from the HXB-2 strain of HIV.

The gp120 amino acid sequence is said to lack cysteine at that position if another amino acid residue is substituted for cysteine that is normally present at that position or if the cysteine is deleted.

The term "wild type" as used in reference to a polypeptide refers to any polypeptide having an amino acid sequence present in a polypeptide from a natural organism, regardless of the source of the molecule, ie the term "wild type" means that the molecule is from a natural source. Purified; Purified after expression using recombinant technology; Or a sequence feature independent of whether it was synthesized.

The term "amino acid sequence variant" refers to a polypeptide having an amino acid sequence that differs from the wild-type amino acid sequence by addition, deletion or substitution of amino acids.

As used herein, the term "conservative amino acid substitutions" means that amino acids are replaced by functionally equivalent amino acids. Functionally equivalent amino acids are generally similar in size and / or properties (eg, charge or hydrophobicity) to the amino acids they replace. Amino acids with similar properties can be classified as follows:

(1) hydrophobic: His, Trp, Tyr, Phe, Met, Leu, Ile, Val, Ala;

(2) neutral hydrophobicity: Cys, Ser, Thr;

(3) polarity: Ser, Thr, Asn, Gln;

(4) acidic / negative charge: Asp, Glu;

(5) charges: Asp, Glu, Arg, Lys, His;

(6) basic / positive charges: Arg, Lys, His;

(7) basic: Asn, Gln, His, Lys, Arg;

(8) residues that affect chain orientation: Gly, Pro; And

(9) aromatic: Trp, Tyr, Phe, His.

The table below shows exemplary and preferred conservative amino acid substitutions.

Original residues Exemplary Conservative Substitutions Preferred Conservative Substitution Ala Val, Leu, Ile Val Arg Lys, Gln, Asn Lys Asn Gln, His, Lys, Arg Gln Asp Glu Glu Cys Ser Ser Gln Asn Asn Glu Asp Asp Gly Pro Pro His Asn, Gln, Lys, Arg Asn Ile Leu, Val, Met, Ala, Phe Leu Leu Ile, Val, Met, Ala, Phe Ile Lys Arg, Gln, Asn Arg Met Leu, Phe, Ile Leu Phe Leu, Val, Ile, Ala Leu Pro Gly Gly Ser Thr Thr Thr Ser Ser Trp Tyr Tyr Tyr Trp, Phe, Thr, Ser Phe Val Ile, Leu, Met, Phe, Ala Leu

A "signal sequence" is an amino acid sequence found on membrane-bound and secreted proteins that is an amino acid sequence that directs the synthesis of proteins into membrane-bound ribosomes and mediates the translocation of the endoplasmic reticulum of the initial peptide chain into the lumen, where the free Various post-translational modifications (eg glycosylation) are available that are not available for the protein synthesized in the cytoplasm on the ribosome. As used in recombinant expression, the polypeptide is secreted from cells expressing the polypeptide into the culture medium for ease of purification. A signal sequence is said to be "heterologous" when it is derived from a polypeptide other than the polypeptide that is fused to promote recombinant expression or secretion.

An "epitope tag" is an amino acid sequence that defines an epitope for an antibody. Epitope tags can be engineered into polypeptides or peptides to facilitate purification or detection.

As used herein, a "fusion polypeptide" is a polypeptide comprising an amino acid sequence from one polypeptide that is linked to an amino acid sequence that is not normally present in the polypeptide to be fused. Amino acid sequences that are not normally present in the polypeptide to be fused may be amino acid sequences (eg, heterologous signal sequences) or artificial sequences from different polypeptides. In general, fusion polypeptides are expressed using recombinant techniques using constructs that contain a nucleotide sequence that encodes one polypeptide sequence fused in frame to a nucleotide sequence that encodes another polypeptide sequence.

The term "derivative" as used in the context of a polypeptide or polypeptide fragment includes amino acid sequence variants as well as any other molecule that differs from the wild type amino acid sequence by addition, deletion or substitution of one or more chemical groups. A "derivative" retains one or more biological or immunological properties of a wild type polypeptide or polypeptide fragment, eg, a biological property that specifically binds to a receptor and an immunological property that specifically binds to an antibody.

"Cell-specific binding moiety" refers to a moiety that specifically binds to a binding partner found in one or many specific cell types. The cell specific binding moiety can be linked to the polypeptide or polynucleotide, for example, to drive the polypeptide or polynucleotide to the desired cell type.

An "immunogenic carrier protein" is a polypeptide that binds to an antigen (ie "hapten") that does not itself elicit a significant immune response. The resulting conjugate can elicit an immune response against hapten.

The term “specific binding” is defined as the binding partner preferentially binding to another partner (eg, two polypeptides, a polypeptide and a nucleic acid molecule, or two nucleic acid molecules) at a particular site. The term “specifically binding” refers to random generation where binding priority (eg, affinity) for a target molecule / sequence lacks a nonspecific target molecule (eg, a specifically recognized site (s). More than 5 times, more preferably 5 times, most preferably 10 times or 20 times.

As used herein, the term "antibody" refers to a protein consisting of one or more polypeptides substantially encoded by an immunoglobulin gene or fragment of an immunoglobulin gene. Recognized immunoglobulin genes include kappa, lambda, alpha, gamma, delta, epsilon and mu constant region genes as well as various immunoglobulin variable region genes. Light chains are classified as kappa or lambda. Heavy chains are classified as gamma, mu, alpha, delta or epsilon, which in turn form IgG, IgM, IgA, IgD and IgE, respectively.

Typical immunoglobulin (antibody) structural units are known to include tetramers. Each tetramer consists of two identical pairs of polypeptide chains, each with one "light" (about 25 kD) chain and one "heavy" chain (about 50-70 kD). The N-terminus of each chain defines the variable region of 100 to 110 or more amino acids primarily responsible for antigen recognition. "Variable light chain (VL)" and "variable heavy chain (VH)" refer to such light and heavy chains, respectively.

Antibodies exist in a number of well characterized fragments produced by degradation by intact immunoglobulins or various peptidase. Thus, for example, pepsin cleaves antibodies under disulfide bonds in the hinge region, producing F (ab) '2, a dimer of Fab, which is itself a light chain that is bound to VH-CH1 by disulfide bonds. to be. F (ab) '2 can convert (Fab') 2 dimers to Fab 'monomers by reducing them to disrupt disulfide bonds in the hinge region under mild conditions. Fab 'monomers are essentially Fabs with a portion of the hinge region (for more detailed descriptions of other antibody fragments, see Fundamental Immunology, W.E. Paul, ed., Raven Press, N.Y. (1993)). Although various antibody fragments are defined in terms of the degradation of intact antibodies, one of ordinary skill in the art will recognize that such Fab ′ fragments can be newly synthesized chemically or by using recombinant DNA methods. Thus, the term antibody as used herein also encompasses antibody fragments produced by modification of the entire antibody or newly synthesized using recombinant DNA methods. Preferred antibodies are single chain antibodies (antibodies present as a single polypeptide chain) in which the variable heavy and variable light chains are joined together (directly or via a peptide linker) to form a continuous polypeptide, more preferably a single chain Fv antibody (sFv or scFv). Single chain Fv antibodies are covalently linked VH-VL heterodimers, which can be expressed from nucleic acids comprising VH- and VL-encoding sequences that are directly bound or bound by peptide encoding linkers (Huston, et al. (1988). Proc. Nat. Acad. Sci. USA, 85: 5879-5883). VH and VL are joined to form a single polypeptide chain, while VH and VL domains are non-covalently linked. Numerous other structures are known to those of skill in the art to convert light and heavy chain polypeptides from scFv antibodies and naturally aggregated but chemically isolated antibody V regions into molecules that are folded into a three-dimensional structure substantially similar to that of the antigen binding site. (See US Pat. Nos. 5,091,513, 5,132,405 and 4,956,778).

The expression “effective amount” and “sufficient amount” means the amount of biologically active substance that produces the intended biological activity.

The term "pharmaceutically acceptable" means any agent that is sufficiently nontoxic to cells and / or subjects to enable pharmaceutical use of the agent.

The term "adjuvant" refers to a compound or mixture that enhances an immune response to an antigen.

A "primary isolate" of HIV is an HIV isolate obtained from an individual infected with HIV without passage of cell culture.

The term "polynucleotide" refers to a deoxyribonucleotide or ribonucleotide polymer and includes known analogs of natural nucleotides that can function in a manner similar to natural nucleotides, unless otherwise defined. The term "polynucleotide" includes, for example, genomic DNA; Complementary DNA (cDNA), which is a DNA representation of mRNA, usually obtained by reverse transcription or amplification of messenger RNA (mRNA); DNA molecules produced synthetically or by amplification; And any form of DNA or RNA, including mRNA. The term "polynucleotide" includes single stranded molecules as well as double stranded nucleic acid molecules. In double stranded polynucleotides, the polynucleotide strands do not need to be coextensive (ie, the double stranded polynucleotides need not be double stranded along the entire length of both strands).

As used herein, the term "vector" refers to a DNA construct containing a polynucleotide. Preferred vectors can be propagated stably or temporarily in host cells. For example, the vector can be a plasmid, cosmid, bacterial artificial chromosome (BAC), yeast artificial chromosome (YAC), or viral vector. When introduced into a suitable host, the vector can replicate and function independently of the host genome, or in some cases can be inserted into the host genome.

As used herein, the term "operably linked" means operatively binding between a regulatory sequence (typically a promoter) and a linked sequence. For example, if a promoter can initiate transcription of a bound sequence, the promoter is operably linked to the sequence.

By "expression vector" is meant a DNA construct containing a polynucleotide operably linked to a regulatory sequence capable of carrying out the expression of the polynucleotide in a suitable host. Exemplary regulatory sequences include promoters for performing transcription, any operator sequence for regulating transcription, sequences encoding suitable mRNA ribosomal binding sites, and sequences regulating termination of transcription and translation.

The term "host cell" refers to a cell capable of temporarily or stably maintaining a vector. Host cells of the invention include, but are not limited to, bacterial cells, yeast cells, insect cells, plant cells, and mammalian cells. Other hosts known in the art are also suitable for use in the present invention.

Host cells may be present in cell culture or, alternatively, may be “in vivo”. When a host cell is present in a living organism, it is called "in vivo."

The term “complementary,” as used herein, refers to the ability of two nucleotides to exactly pair. That is, if a nucleotide at a given position of a nucleic acid molecule can hydrogen bond with a nucleotide of another nucleic acid molecule, these two nucleic acid molecules are considered to be complementary to each other at that position. The term “substantially complementary” refers to a sequence that is sufficiently complementary to other sequences so that it can specifically hybridize under stringent hybridization conditions.

The phrase “strict hybridization conditions” generally means a temperature about 5 ° C. below the melting point (T _m ) for the specific sequence at the defined ionic strength and pH. Exemplary stringent conditions suitable for achieving specific hybridization of most sequences are salt concentrations of about 0.2 molar at temperatures of about 60 ° C. or higher and pH 7.0.

"Specific hybridization" means that a nucleic acid molecule binds to a target nucleotide sequence in the absence of substantial binding to other nucleotide sequences present in the hybridization mixture under defined stringent conditions. Those skilled in the art recognize that mitigating the stringency of hybridization conditions can tolerate sequence mismatches.

Isolated gp120 polypeptide with abnormal disulfide structure

The present invention provides an isolated polypeptide comprising a first gp120 amino acid sequence. An isolated polypeptide may comprise one or more additional sequences and thus the isolated polypeptide may comprise a full length gp160 sequence or a gp120 sequence containing fragment of gp160. The first gp120 sequence may be the full length gp120 sequence or fragment thereof. Gp120 fragments useful in the present invention include at least the V2, V3 and C4 domains of gp120. In a preferred embodiment, the gp120 fragment also comprises a V1 domain. The gp120 sequence lacks one or more of the 18 cysteine residues present in most gp120 sequences, or includes one or more additional cysteines.

The gp120 polypeptide of the invention can be used as a component of an immunogenic composition of the invention to elicit a gp120-specific immune response. In a preferred embodiment, the gp120 polypeptide is used as a vaccine antigen. Polypeptides can be included in the vaccine in various forms, such as free forms, covalently bound to cell specific moieties, or immunogenic carrier proteins, or displayed on the surface of viral particles (viruses Derived vaccine). In addition, gp120 polypeptides that transport drugs can be used to target the drug to CD4- or chemokine receptor-containing cells.

The gp120 polypeptides of the invention are useful in diagnostic methods for determining whether a sample contains antibodies specific for a given gp120 polypeptide having an abnormal disulfide structure.

In addition, suitable polypeptides of the invention can be used as standards in the gp120 immunoassay. More specifically, polypeptides of the invention that cross react with anti-HIV-1 antibodies used in the immunoassay can be used as positive controls, which are compared with the results observed when the sample is assayed for the presence of gp120. Can be.

A. Types of gp120 Polypeptides

In a first embodiment, the first gp120 sequence is numbered from the N-terminal methionine of gp120 from the HXB-2 strain of HIV gp120 to 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239 At least one of the positions 247, 296, 331, 378, 385, 418 and 445 is missing one or more cysteine residues. In a preferred variation of this embodiment, the first gp120 sequence lacks one or more cysteine residues at one or more positions of 54, 74, 119, 126, 157, 205, 218, 228, 239, 247, 331, 378 and 385 have.

In a second embodiment, the first gp120 sequence is numbered based on HXB-2 gp120 to be 24, 29, 34, 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, One or more additional cysteine residues at positions other than 296, 331, 378, 385, 418, 445, 493, 495, 499-501, 503-508 and 510. However, the first gp120 sequence of the present invention is not a subtype G gp120 sequence with one or more additional cysteines in the V1 domain, nor is it a subtype E gp120 sequence with one or more additional cysteines in the V4 domain. In a preferred variation of this embodiment, the first gp120 sequence is other than 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 297, 331, 378, 385, 418 and 445 One or more additional cysteine residues in position, provided that one or more additional cysteine residues are not present in the V1 domain of gp120.

The present invention also combines these two embodiments, i.e., the first gp120 sequence lacks one or more cysteines at the positions described in the first embodiment, and includes one or more additional cysteines at the positions described in the second embodiment. It involves doing.

In a preferred embodiment, the first gp120 sequence comprises SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134 and 136 Have at least about 80%, about 85%, about 90%, about 95%, or about 99% identity to each of the V2, V3, and C4 domains of the gp120 sequence selected from the group consisting of: These gp120 sequences were obtained from large scale clinical trials of HIV vaccines carried out in 61 clinical sites across North America, Puerto Rico and the Netherlands. Table 1 below shows the corresponding between SEQ ID NO and gp120 sample design from the experiment. The amino acid sequence for gp120 from the HXB-2 strain of HIV-1 is SEQ ID NO: 138.

In a more preferred embodiment, the first gp120 sequence is at least about 80%, about 85%, about 90%, about 95% or about 99% to each of the V1, V2, V3 and C4 domains of the gp120 sequence selected from one of these sequences Have identity. This requirement is met if the percent identity for each of these domains is at least about 80%, about 85%, about 90%, about 95% or about 99%. The endpoints of these domains, numbered from the N-terminal methionine of HXB-2, are as follows: V1: residues 131-157; V2: residues 157 to 196; V3: residues 296 to 331; C4: residues 418 to 445. In certain examples of this embodiment, the first gp120 sequence is SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 , 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78 , 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128 At least V1, V2, V3 and C4 domains of the gp120 sequence selected from the group consisting of 130, 132, 134 and 136.

Table 1. Sequence ID numbers for HIV-1 gp120 DNA and protein sequences

The gp120 amino acid sequence may be a native (ie wild type) amino acid sequence or an amino acid sequence variant of the corresponding region of a wild type polypeptide. In one embodiment, the gp120 amino acid sequence is derived from the primary isolate of HIV-1. Preferred polypeptides of the invention generally comprise a wild type gp120 amino acid sequence or a gp120 amino acid sequence containing conservative amino acid substituents as defined above.

Polypeptides of the invention may comprise other amino acid sequences in addition to the gp120 amino acid sequence, ie, the amino acid sequence from the heterologous protein. Thus, the invention includes fusion polypeptides in which the gp120 amino acid sequence is fused from one or more heterologous proteins to one or both ends of the amino acid sequence. Examples of additional amino acid sequences that are often incorporated into the protein of interest include signal sequences that promote secretion of the protein, and epitope tags that can be used for immunological detection or affinity purification. Preferred signal sequences used in the present invention include, but are not limited to, herpes simplex virus glycoprotein D (HSV gD-1) signal sequence and human tissue plasminogen activator signal sequence. Exemplary epitope tags include green fluorescent protein, hemagglutinin, or FLAG epitope tags and hexahistidine or similar metal affinity tags. N-terminal HSV gD-1 sequences are commonly used as epitope tags when the HSV gD-1 signal sequence is used to promote secretion.

Polypeptides of the invention can be modified to produce derivatives that retain the ability to induce a gp120-specific immune response. For example, to those skilled in the art, various techniques have the same or different desired biological activities as the corresponding peptide compounds, and are more advantageous than peptides, for example in solubility, stability and sensitivity to hydrolysis and proteolysis. It is obvious that it is useful for constructing a so-called "peptide mimetic" having. See, eg, Morgan, et al., Ann. Rep. Med. Chem., 24: 243-252 (1989). Thus, polypeptides of the invention include peptide mimetics, for example, modified at N-terminal amino groups, C-terminal carboxyl groups and / or at least one amido bond of the peptide is converted to nonamido bonds.

In certain embodiments, polypeptides of the invention comprise a first gp120 sequence having an odd cysteine residue. Such sequences have one or more "free" cysteines (ie, cysteines that do not form intermolecular disulfide bonds). Free cysteine can covalently bind other polypeptides. For example, free cysteine can form disulfide bonds with free cysteine in other polypeptides. The free cysteine can easily be inserted into any subject polypeptide, for example using site specific mutagenesis. The other polypeptide may comprise a first gp120 sequence, which may be the same as or different from the first gp120 sequence. Disulfide bonds between two identical gp120 sequences result in homodimers. Disulfide bonds between two different gp120 sequences produce heterodimers.

In a variation of this embodiment, the cysteine liberated in the first gp120 sequence binds covalently to another polypeptide comprising the gp41 amino acid sequence. Preferably, the first gp120 sequence disulfides to the cysteine liberated in the gp41 sequence to produce a gp120 / gp41 complex. Such complexes are useful as antigens because they can mimic the gp120 / gp41 complex found in viral spikes on the surface of HIV-1 virus particles or virus infected cells.

In other embodiments, the cysteine liberated in the gp120 sequence covalently binds to cell specific binding moieties, drugs, immunostimulatory oligonucleotides (eg, CpG) or immunogenic carrier proteins. Targeting gp120 derived in this manner to antigen-presenting cells (eg dendritic cells or macrophages) may be useful for modulating the efficacy and properties of an immune response (eg, a TH1 or TH2 immune response). Cell-specific binding moieties useful in the present invention are specific ligands located in target cells or cells (eg leukocytes) but not found in significant amounts in non-target cells (eg liver or muscle cells). -Moieties capable of binding to binding sites (eg ligands or fragments thereof). Generally, cell specific binding moieties bind to membrane-bound cell-surface proteins, carbohydrates, lipids, glycosaminoglycans, lipoproteins, antigens or receptors. As such, exemplary cell-specific binding moieties may include, for example, ligands such as hormones or cytokines, receptor binding domains of hormones or cytokines, adhesion molecules and antibodies. Commonly used immunogenic carriers suitable for use in the present invention include diphtheria toxin, keyhole limpet hemocyanin (KLH), tyroglobulin, bovine serum albumin (BSA) and tetanus toxin.

B. Generation of gp120 Polypeptides

1. Synthesis Technique

Polypeptides according to the invention can be synthesized using methods known in the art such as exclusive solid phase synthesis, partial solid phase synthesis, fragment condensation, and classical solution synthesis. See, eg, Merrifield, J. Am. Chem. Soc., 85: 2149 (1963). Solid phase techniques are preferred and are described, for example, in John Morrow Stewart and Janis Dillaha Young, Solid Phase Peptide Syntheses (2nd Ed., Pierce Chemical Company, 1984). At the solid phase, the synthesis is typically initiated from the C-terminus of the peptide using alpha-amino protected resins. Suitable starting materials can be prepared, for example, by attaching the required alpha-amino acids to chloromethylated resins, hydroxymethyl resins or benzhydrylamine resins. Automated peptide synthesizers are commercially available as they serve to align peptides.

2. Recombination Technique

Polypeptides according to the invention can also be produced using recombinant techniques. gp120 polynucleotides are synthetically generated or amplified from viral RNA, proviral DNA or cloned gp120 polynucleotides or HIV-1 isolates by (PCT, RT-PCT, rolling circle amplification (RCA) or other amplification methods) Or cloned from an HIV-1 isolate. On the other hand, with the provided gp120 polynucleotides, the polynucleotides encoding the desired gp120 amino acid sequence can be produced by various cloning and mutagenesis. See, eg, Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989) in Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor, N.Y. Examples of widely used mutagenesis include site-specific mutagenesis (Kunkel et al., (1991) Methods Enzymol., 204: 125-139; Carter, P., et al., (1986) Nucl. Acids Res. 10 : 6487), cassette mutagenesis (Wells, JA, et al., (1985) Gene 34: 315), and restriction selection mutagenesis (Wells, JA, et al., (1986) Philos. Trans.R.Soc. , London Ser.A, 317: 415.

In a preferred embodiment of the invention, the sequence of the gp120 coding region is used as a guide for designing synthetic polynucleotides encoding the desired gp120 sequence, which synthetic polynucleotides can be incorporated into the vectors of the invention. Methods for constructing synthetic genes are well known to those skilled in the art. See, eg, Dennis, M.S., Carter, P. and Lazarus, R.A. (1993) Proteins; Struct. Funct. Genet., 15: 312-321. Expression and purification methods are described in more detail below in connection with the nucleic acids, vectors and host cells of the present invention.

3. Composites and Conjugates

The gp120 polypeptides of the invention can be modified by the techniques generally used to generate polypeptide complexes and conjugates. Disulfide-linked oligomeric complexes comprising one or more gp120 polypeptides may, for example, contain mild reducing agents such as glutathione, dithiothritol (DTT) or β-mercaptoethanol and optionally denaturing agents such as urea or guanidine hydrochloride. It can be produced by mixing polypeptides that will form complexes in the solution containing them. Reducing agents and selective denaturants can be removed by dialysis. Disulfide bonds are formed during denaturation in air, which oxidizes the reduced sulfhydryl group. Intramolecular disulfide bonds produce oligomers. If the solution contains only one type of gp120 polypeptide, the oligomers formed will contain only such species. If the solution contains different gp120 polypeptides or gp120 polypeptides along with other polypeptides (eg gp41), the oligomers formed may contain various species.

Alternatively, oligomeric complexes comprising one or more gp120 polypeptides of the invention can be produced using, for example, standard difunctional crosslinkers. Such agents can also be used to generate conjugates of gp120 polypeptide with cell-specific binding moieties, drugs, immunostimulatory oligonucleotides, or immunogenic carrier proteins.

In some applications, such as in the clinical methods described below, it is desirable to attach a detectable label to one gp120 polypeptide or gp120 polypeptides of the invention. Detectable labels suitable for use in the present invention include compositions detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means. Examples include labeled streptavidin conjugates, magnetic beads (e.g., Dynabeads ^TM ), fluorescent dyes (e.g., fluorescein, Texas red, rhodamine, coumarin, oxazine, green fluorescent protein See, eg, Molecular Probes, Eugene, Oregon, USA), radiolabels (eg, ³ H, ¹²⁵ I, ³⁵ S, ¹⁴ C or ³² P), enzymes (eg horse radish) Peroxidase, alkaline phosphatase and other enzymes commonly used in ELISA), and colorimetric labels such as colloidal gold (eg, gold particles with high efficiency scatter green light of 40-80 mm diameter) or colored glass Or biotin for dyeing with plastic (eg, polystyrene, polypropylene, latex, etc.) beads. Patents teaching the use of such labels are described in US Pat. 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149; And 4,366,241.

Protein polynucleotides, vectors, and host cells that encode gp120 polypeptides with abnormal disulfide structures

The invention also provides an isolated polynucleotide encoding a polypeptide of the invention. Thus, the polynucleotides of the present invention comprise DNA or RAN moieties that encode the gp120 amino acid sequence. Polynucleotides of the invention are useful for the production of recombinants of polypeptides of the invention in vivo (ie, organisms) or in vitro (eg, cell cultures). In certain embodiments, as described below, the polynucleotides of the present invention may be used in immunogenic compositions such as DNA vaccines, recombinant viruses or virus derived vaccines (ie, as components of viral particles). In addition, the gp120 polynucleotides of the present invention can be used in clinical methods to determine whether a sample contains a polynucleotide encoding a gp120 polypeptide having an abnormal disulfide structure.

A. Polynucleotides

In certain embodiments, the polynucleotides comprise SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, Group consisting of 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134 and 136 Encode a gp120 sequence having at least about 80%, about 85%, about 90%, about 95% or about 99% identity to each of the V1, V2, V3 and C4 domains of gp120 selected from. In a preferred embodiment, the polynucleotides comprise SEQ ID NO; 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, Gp120 nucleotide sequence selected from the group consisting of 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135 or subsequences thereof Wherein the sequence encodes at least the V1, V2, V3 and V4 domains of gp120. Table 1 above shows the correspondence between gp120 sample design and SEQ ID NO from the clinical trials discussed above. The nucleotide sequence for gp120 from the HXB-2 strain of HIV-1 is SEQ ID NO: 137.

As discussed above, the encoded gp120 amino acid sequence may be a wild type sequence or a variant sequence. If the gp120 amino acid sequence is a wild type sequence, the nucleotide sequence encoding such a sequence may be a nucleotide sequence or wild type nucleotide sequence containing one or more "silent" mutations that do not induce amino acid sequence modifications due to degeneracy of the genetic code.

For example, when the polynucleotide is for use in expressing an encoded polypeptide, the silent variant can be introduced by standard mutagenesis that optimizes the codon as desired by the host cell. Alternatively, polynucleotides containing silent variants can be designed and synthesized. More particularly, as those skilled in the art, the use of codons is highly irregular and differs between species. Codon usage patterns are known to be related to the relative abundance of tRNA isoacceptors. For gp120, changes in codon frequency are known to enhance recombinant production of gp120 in mammalian cells (Haas J et al. (1996) Curr Biol. 6 (3): 315-24: Andre S. et. al. (1998) J Virol. 72 (2): 1497-503). Native gp120 coding sequences generally exceed 60% A-T and highly expressed genes in mammalian systems tend to exceed about 60% G-C. Thus, where the polynucleotides of the invention are useful for expressing the polypeptides of the invention in mammalian cells, the polynucleotides are preferably found in mammalian genes with codon frequencies more preferably in relatively highly expressed mammalian genes. "Codon-optimized" to more closely match the codon frequency that is being obtained.

Codon-optimized polynucleotides of the invention are typically about 50% to about 80% different from the nucleotide sequence from their unoptimized counterparts. Thus, the codon-optimized polynucleotides of the present invention may share about 50%, about 60%, about 70%, about 80%, or about 90% sequence identity with the corresponding non-optimized polynucleotide.

In a preferred embodiment, the polynucleotides of the invention are codon-optimized for expression in mammalian cells. Particularly advantageous are rodent cells (eg mouse, rat and hamsper cells) and primate cells (eg monkey or human cells). For example, in a preferred embodiment, the polynucleotides of the invention are codon-optimized for expression in Chinese Hamsper Ovary (CHO) cells. The polynucleotides of the invention can be codon-optimized based on any gene from the species in which expression is desired, but codon-optimization preferably changes the codon frequency close to the codon frequency of a relatively highly expressed gene. Is performed. For example, the polynucleotides of the present invention may have a codon frequency close to the codon frequency of an immunoglobulin gene. As such, for example, codon frequencies of human Ig kappa and Mu constant region genes can be determined, and polynucleotides can be engineered to have codon frequencies close to the combined codon frequencies of Ig kappa and Mu constant region genes. For simplicity, the sequence of such genes can be downloaded from genebanks or similar databases. The Ig kappa C-region is designed as position HUMIGKC3 of the gene bank and the Ig Mu C-region sequence is designed as position HSIGMHCC. These sequences are then copied and codon usage is determined. Codon usage information can be combined and the combined codon frequency is calculated. Codon-optimized polynucleotides of the present invention having codon frequencies that substantially match the combined codon frequencies for the Ig gene are then produced synthetically conveniently.

In some applications, it is advantageous to produce polynucleotides that have been modified to more suitably suit a particular application or to stabilize the polynucleotides described herein. To this end, the polynucleotides of the present invention contain phosphorothioates, phosphoesters, methyl phosphonates, short chain alkyl or cycloalkyl intersugar bonds or short chain heteroatoms or heterocyclic sugar ("backbone") bonds. can do. Most preferred are phosphorothioates, CH2--NH--O--CH2, CH2--N (CH3)-O--CH2 (known as methylene (methylimino) or MMI backbone) and CH2- Phosphorothioate with -O--N (CH3)-CH2, CH2--N (CH3)-N (CH3)-CH2, and O--N (CH3)-CH2--CH backbone Where the phosphodiester is O--P--O--CH2. Also preferred are polynucleotides having a morpholino backbone structure (Summerton, J.E. and Weller, D.D., U.S. Pat.No. 5,034,506). Other preferred embodiments use a protein-nucleic acid or peptide-nucleic acid (PNA) backbone, wherein the phosphodiester backbone of the polynucleotide is replaced with the polyamide backbone, and the base is directly or indirectly to the aza nitrogen atom of the polyamide backbone. (PE Nielsen, M.Egholm, RHBerg, O.Buchardt, Science 1991, 254, 1497). The polynucleotides of the present invention may contain alkyl and halogen-substituted sugar moieties and / or may have sugar mimetics such as cyclobutyl instead of pentofuranosyl groups. In other preferred embodiments, the polynucleotide may comprise one or more modified base forms or “common bases” such as inosine. Polynucleotides may include, as necessary, groups for enhancing the pharmacokinetic properties of RNA cutters, cholesteryl groups, acceptor groups, intercalators, polynucleotides, and / or groups for enhancing the pharmacokinetic properties of polynucleotides. .

In addition, the polynucleotides of the present invention may be modified to include various available labels for use in hybridization assays. Suitable labels include the labels discussed above for gp120 polypeptide labeling of the invention. Fluorescent molecules are conveniently used to label polynucleotides for use in clinical methods. Fluorescent labels capable of binding to polynucleotides include, but are not limited to, fluorescein, Texas red, rhodamine, coumarin, oxazine, green fluorescent protein.

Those skilled in the art understand that polynucleotides complementary or substantially complementary to the coding strand of the polynucleotides of the present invention can be used to inhibit the expression of the polypeptides of the present invention, which may be advantageous for research or therapeutic purposes. Thus, nucleic acids of the present invention include such "antisense polynucleotides" and the phrase "polynucleotides encoding a polypeptide of the present invention" is interpreted to include such antisense molecules. Antisense polynucleotides can be DNA or RNA, and are useful for research or therapeutic antisense or RNA interference (RNAi) applications, respectively.

Polynucleotides of the invention can be synthesized, amplified from cloned gp120 polynucleotides or HIV-1 isolates, or obtained from HIV-1 isolates. If desired, the nucleotide sequence of the polynucleotide thus obtained can be modified using various cloning and mutagenesis to reach the desired nucleotide sequence. See, eg, Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989) in Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor, N.Y.

B. Vector

Polynucleotides of the invention can be incorporated into vectors for propagation and / or expression in host cells. Such vectors are typically replicating sequences (ie, replication origins) and selectable markers such as antibody resistance that can perform replication of the vector in a suitable host cell (eg, E. coli, Chinese hamster ovary [CHO] cells). It contains a sequence that encodes a gene. Upon transformation of a suitable host, the vector may independently replicate and function independently of the host genome or may be inserted into the host genome. Vector design depends, among other things, on the intended use, and designs of host cells for vectors, and vectors of the invention for particular uses and host cells, are within the scope of the art.

If the vector is for expression of a polypeptide, the vector comprises one or more regulatory sequences capable of inducing and / or augmenting the expression of an operably linked polypeptide-coding sequence. For example, regulatory sequences suitable for expression of prokaryotes may include promoter sequences, operator sequences, and ribosomal binding sites. Regulatory sequences for expression in eukaryotic cells may include promoters, enhancers and transcription termination sequences (ie, polyadenylation signals). Expression vectors of the invention are useful for expressing polypeptides of the invention in vivo (eg, DNA or virus derived vaccine applications) or in vitro (eg, cell culture).

All expression vectors according to the invention may also comprise other sequences such as signal sequences or nucleic acid sequences encoding proliferable genes. The signal sequence can secrete the polypeptide fused to it in a cell expressing the protein. In expression vectors, the nucleic acid encoding the signal sequence is linked to the coding sequence to preserve the reading frame of the coding sequence. In addition, the inclusion of a gene vector in a selected host cell that compensates for dystrophic deficiency allows selection of a host cell transformed with the vector.

Viral vectors are particularly useful for inducing the polynucleotides of the invention into cells or organisms and then expressing the encoded proteins. Viral vectors have been extensively studied as means for delivering polypeptides to organisms to ameliorate physiological diseases, ie, "gene therapy." For a review of gene therapy processes, see, eg, Anderson, Science (1992) 256: 808-813; Nabel and Felgner (1993) TIBTECH 11: 211-217; Mitani and Caskey (1993) TIBTECH 11: 162-166; Mulligan (1993) Science, 926-932; Dillon (1993) TIBTECH 11: 167-175; Miller (1992) Nature 357: 455-460; Van Brunt (1988) Biotechnology 6 (10): 1149-1154; Vigne (1995) Restorative Neurology and Neuroscience 8: 35-36; Kremer and Perricaudet (1995) British Medical Bulletin 51 (1) 31-44; Haddada et al. (1995) in Current Topics in Microbiology and Immunology, Doerfler and Boehm (eds) Springer-Verlag, Heidelberg Germany; and Yu et al., (1994) Gene Therapy, 1: 13-26.

Widely used viral vector systems include, but are not limited to, adenoviruses, adeno-associated viruses, vaccinia viruses, canariadu viruses, herpes viruses, and various retroviral expression systems. The use of adenovirus vectors is well known to those skilled in the art and is described in detail, for example, in WO 96/25507. Particularly preferred adenovirus vectors are described in Wills et al. (1994) Hum. Gene Therap. 5: 1079-1088. Adenovirus vectors suitable for use in the present invention are also commercially available. For example, the Adeno-X ^™ Tet-Off ^™ gene expression system sold by Clontech provides an effective means of introducing inducible heterologous genes into most mammalian cells.

For example, adeno-associated virus (AAV) -based vectors used in in vitro production of polynucleotides and peptides and in cells transduced with target nucleic acids in in vivo and ex vivo gene therapy processes are described, for example, in West. et al. (1987) Virology 160: 38-47; Carter et al. (1989) U.S. Patent No. 4,797,368; Carter et al. WO 93/24641 (1993); Kotin (1994) Human Gene Therapy 5: 793-801; Muzyezka (1994) J. Clin. Invst. 94: 1351; Lebkowski, U.S. Pat. No. 5,173,414; Tratschin et al. (1985) Mol. Cell. Biol. 5 (11): 3251-3260; Tratschin, et al. (1984) Mol. Cell. Biol., 4: 2072-2081; Hermonat and Muzyczka (1984) Proc. Natl. Acad. Sci. USA, 81: 6466-6470; McLaughlin et al. (1988) and Samulski et al. (1989) J. Virol., 63: 03822-3828. Cell lines that can be transformed with rAAV are described by Lebkowski et al. (1988) Mol. Cell. Biol., 8: 3988-3996.

Widely used retroviral vectors include murine Lucemia virus (MuLV), Gibbon-Apes Leukemia Virus (GaLV), monkey immunodeficiency virus (SIV), human immunodeficiency virus (HIV), alphavirus, and combinations thereof. Vectors based (see, eg, Buchscher et al. (1992) J. Virol. 66 (5) 2731-2739; Johann et al. (1992) J. Virol. 66 (5): 1635-1640). (1992); Sommerfelt et al., (1990) Virol. 176: 58-59; Wilson et al. (1989) J. Virol. 63: 2374-2378; Miller et al., J. Virol. 65: 2220- 2224 (1991); Wong-Staal et al., PCT / US94 / 05700, and Rosenburg and Fauci (1993) in Fundamental Immunology, Third Edition Paul (ed) Raven Press, Ltd., New York and the reference therein, and Yu et al. (1994) Gene Therapy, supra; US Patent 6,008,535, and the like). Other suitable viral vectors include, but are not limited to, herpes simplex virus (HSV), papillomavirus, Epstein Barr virus (EBV), and lentivirus.

In one embodiment, the vector according to the invention is a bifunctional plasmid that can act as a DNA vaccine and a recombinant viral vector. Direct injection of purified vector DNA into a subject, ie, a DNA vaccine, induces an immune response against the encoded polypeptide. Vectors can also be used to generate live recombinant viruses for use in virus derived vaccines. Such vectors contain nucleotide sequences encoding polypeptides of the invention that are operably linked to two different promoters, an animal promoter (for use as a vector in a DNA vaccine) and a viral promoter (for use in a virus derived vaccine). Include.

The vector of the present invention is generated by binding the desired element by ligation at an appropriate restriction site. If such sites do not exist, suitable sites may be inserted by standard mutagenesis (eg, site specific or cassette mutagenesis), or synthetic oligonucleotide adapters or linkers may be used in accordance with conventional practice.

C. Host Cells

The invention also provides host cells containing the vectors of the invention. A wide variety of host cells are useful for propagation and / or expression of vectors. Examples include prokaryotic cells (e.g., E. coli and Bacillus, Pseudomonas and other bacterial strains), yeast or other fungal cells (including S. cerevisiae and P. pastoris), insect cells, plant cells, and phages. But also eukaryotic cells, including mammalian cells (eg, Chinese hamster ovary cells), in particular human cells (eg, human embryonic kidney cells). Host cells according to the present invention include culture cells and cells present in living organisms, such as transgenic plants or animals or cells into which a DNA vaccine or viral vector has been inserted.

The vector of the present invention is introduced into the host cell by any suitable method that will vary depending on the vector-host system used. In general, vectors are introduced into host cells by transformation (also known as "transfection") or infection with a virus containing the vector. If the host cell is a prokaryotic cell (or carrier cell with a cell wall), suitable transformation methods are described in Cohen, et al. (1972) Proc. Natl. Acad. Sci., USA, 69: 2100-14. When prokaryotic cells are used as hosts and the vector is a phagemid vector, each vector can be introduced into the host cell by infection. Yeast cells are described, for example, in Hinnen (1978) Proc. Natl. Acad. Sci, USA, 75: 1929-33, can be used to transform using polyethylene glycol. Mammalian cells are described in Graham, et al. (1978) Virology, 52: 546 and Gorman, et al. (1990) DNA and Prot. Eng. Tech., 2: 3-10] can be conveniently transformed using the calcium phosphate precipitation method described. However, other known methods for introducing DNA into host cells such as nuclear injection, electroporation and protoplast fusion can be used in the present invention.

The present invention includes introducing a vector of the present invention into cells in vivo and cells in vitro, ie culture cells. Techniques for inserting vectors into cells present in living organisms are well known and described in more detail below in connection with the use of the immunogenic compositions of the invention. In certain embodiments, a vector of the invention is inserted into a subject in a DNA or virus derived vaccine.

Recombinant production method

Host cells transformed with expression vectors can be used to express polypeptides encoded by the polynucleotides of the invention. Expression involves culturing the host cell under conditions suitable for cell growth and expression, and recovering the expressed polypeptide from the cell lysate or from the culture medium when the polypeptide is secreted. In particular, the culture medium contains suitable nutrients and growth factors for the host cells used. Nutrients and growth factors are well known in many cases, or can be readily determined experimentally by one skilled in the art. For example, suitable culture conditions for mammalian host cells are described in Mammalian Cell Culture (Mather ed., Plenum Press 1984) and in Barnes and Sato (1980) Cell 22: 649.

In addition, the culture conditions should allow for transcription, translation and protein transport between cell compartments. Factors affecting this process are well known and include, for example, the number of DNA / RNA copies; Factors that stabilize DNA; Nutrients, supplements, and transcription inducers or refreshers present in the culture medium; Temperature, pH and osmolality of the culture; And cell density. Regulation of these factors to promote expression in certain vector-host cell systems is within the level of those skilled in the art. For example, principles and practice techniques for maximizing the productivity of in vitro mammalian cell culture can be found in Mammalian Cell Biotechnology: a Practical Approach (Butler ed., IRL Press (1991)).

Many well known techniques for large or small scale protein production can be used to express polypeptides of the invention. This includes, but is not limited to, the use of shaked flasks, fluorinated bed bioreactors, roller bottle culture systems, and stirred tank bioreactor systems. Cell culture can be performed in batch, fed-batch or continuous mode.

Methods for recovering the recombinant protein produced as described above are well known and depend on the expression system used. Polypeptides comprising the signal sequence can be recovered from the culture medium or from the periplasm. Polypeptides can also be expressed intracellularly and recovered from cell lysates.

The expressed polypeptide can be purified from the cell culture or cell lysate by any method capable of separating the polypeptide from one or more components of the host cell or culture medium. Typically, a polypeptide is isolated from host cell and / or culture medium components that are in conflict with the intended use of the polypeptide. As a first step, the culture medium or cell lysate is generally centrifuged or filtered to remove cell debris. The supernatant is then centrifuged, diluted to the desired volume, or diafiltered with a buffer suitable for conditioning the preparation for further purification.

The polypeptide can then be further purified using well known techniques. The technique chosen will depend on the nature of the expressed polypeptide. For example, when a polypeptide is expressed as a fusion protein containing an epitope tag or other affinity domain, purification typically involves the use of an affinity column containing a cognate binding partner. For example, a polypeptide fused with a green fluorescent protein, hemagglutinin or FLAG epitope tag, or hexahistidine or similar metal affinity tag can be purified by segmentation on an affinity column.

Immunogenic Compositions

A. Types of Immunogenic Compositions

Immunogenic compositions of the invention may comprise an isolated polypeptide of the invention, an isolated polynucleotide, or both. The isolated gp120 polypeptide of the present invention is present in the immunogenic composition in an amount sufficient to induce an anti-gp120 immune response when administered to a subject at a suitable dose. The isolated gp120 polynucleotide of the present invention is present in the immunogenic composition in an amount sufficient for administration of a suitable dose to the subject induces expression of the encoded gp120 polypeptide, thereby stimulating an anti-gp120 immune response.

In a preferred embodiment, the immunogenic composition is "multivalent", which provides two or more different antigenic gp120 sequences. As such, the polypeptide based composition may contain one or more polypeptides comprising a gp120 sequence derived from two or more different HIV isolates. The polynucleotide based composition may contain one or more polynucleotides encoding a gp120 sequence derived from two or more different HIV isolates. Alternatively, an immunogenic composition of the invention may contain one or more polypeptides comprising a gp120 sequence derived from one HIV isolate and one or more polynucleotides encoding a gp120 sequence derived from a different HIV isolate. Variations of this embodiment can be carried out as many different antigenic gp120 sequences as desired, for example 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50 or 100 or more different antigenic gp120 sequences. Can be provided.

1. Immunogenic Compositions Containing Polypeptides

The present invention provides immunogenic compositions containing the isolated polypeptides of the present invention. The composition optionally contains other components, including, for example, stock solutions such as suitable buffers such as physiological buffers. In a preferred embodiment, the other component is a pharmaceutically acceptable carrier such as that described in Remington's Pharmaceutical Sciences (1980) 16th editions, Osol, ed., 1980.

The immunogenic composition may comprise one or more polypeptides, immunostimulatory oligonucleotides or immunogenic carrier proteins of the invention covalently bound to a free form (ie, non-conjugated to other portions) or to a cell specific binding site. Can be.

In one embodiment, the immunogenic compositions of the invention comprise cells, cell lysates, or fractions thereof containing the polypeptide, such as membrane fractions, that express the polypeptides of the invention.

In another embodiment, the immunogenic composition comprises viral particles and / or virus infected cells representing one or more polypeptides of the invention. Immunization of subjects with engineered viral particles and / or infected cells is well known in the art, and compositions used for immunization are generally referred to as "virus derived vaccines". Virus-derived vaccines may be advantageous because viral infectious components can promote potent immune responses that activate B lymphocytes, helper T lymphocytes, and cytotoxic T lymphocytes. Many viral species can be used to produce recombinant viruses useful for virus derived vaccines. Examples include vaccinia virus (International Patent Publication WO 87/06262, Oct. 22, 1987, by Moss et al .; Cooney et al., Proc. Natl. Acad. Sci. USA 90: 1882-6 (1993); Graham et. al., J. Infect. Dis. 166: 244-52 (1992); McElrath et al., J. Infect. Dis. 169: 41-7 (1994)) and Canarydu virus (Pialoux et al., AIDS Res). Hum.Retroviruses 11: 373-81 (1995), erratum in AIDS Res.Hum.Retroviruses 11: 875 (1995); Andersson et al., J. Infect. Dis. 174: 977-85 (1996); Fries et. al., Vaccine 14: 428-34 (1996); Gonczol et al., Vaccine 13: 1080-5 (1995). Virus derived vaccines can be made using defective adenoviruses or adenoviruses (Gilardi-Hebenstreit et al., J. Gen. Virol. 71: 2425-31 (1990); Prevec et al., J. Infect. Dis. 161: 27-30 (1990); Lubeck et al., Proc. Natl. Acad. Sci. USA 86: 6763-7 (1989); Xiang et al., Virology 219: 220-7 (1996) ). Other viruses that can be engineered to produce recombinant viruses useful in vaccines include retroviruses that are packaged in cells with an amphotropic host range (eg, Miller, Human Gene Ther. 1: 5-14 (1990) Ausubel et al., Current Protocols in Molecular Biology, § 9), and attenuated or defective DNA viruses such as herpes simplex virus (HSV) (see, eg, Kaplitt et al., Molec. Cell. Neurosci. 2: 320-330 (1991)), papillomavirus, Epstein Barr virus (EBV), adeno-associated virus (AAV) (see, eg, Samulski et al., J. Virol. 61: 3096-3101 (1987); see Samulski et al., J. Virol. 63: 3822-3828 (1989), and the like.

Pharmaceutically acceptable carriers suitable for use in the present invention are nontoxic to cells, tissues or subjects at the dosages employed, and include buffers (eg, buffers made of phosphate buffers, citrate buffers, and other organic acids), antioxidants Agents (eg, ascorbic acid), low molecular weight (less than about 10 residues) peptides, polypeptides (eg, serum albumin, gelatin, and immunoglobulins), hydrophilic polymers (eg, polyvinylpyrrolidone), amino acids (eg, Glycine, glutamine, asparagine, arginine and / or lysine), monosaccharides, disaccharides and / or other carbohydrates (including glucose, mannose and dextrins), chelating agents (eg, ethylenediaminetetraacetic acid [EDTA]) Sugar alcohols (eg mannitol and sorbitol), salt-forming counterions (eg sodium) and / or anionic surfactants (eg Tween ^™ , Pluronics ^™ , and PEG). In one embodiment, the pharmaceutically acceptable carrier is an aqueous pH-buffered solution.

Preferred embodiments include sustained release compositions. Exemplary sustained release compositions include semipermeable matrices of solid hydrophobic polymers to which the polypeptide is attached or the polypeptide is encapsulated. Examples of suitable polymers include polyesters, hydrogels, polylactides, copolymers of L-glutamic acid and T-ethyl-L-glutamease, nondegradable ethylene-vinylacetate, degradable lactic acid-glycolic acid copolymers, and Poly-D-(-)-3-hydroxybutyric acid. Such materials are present in the form of specified articles such as films or microcapsules.

Examples of sustained release compositions typically include a polypeptide attached to a polyalkylene glycol (eg, polyethylene glycol [PEG]) via an ε-amino group. PEG attachment to proteins is a well known means of extending half-life in vivo (see, eg, Abuchowski, J., et al. (1977) J. Biol. Chem. 252: 3582-86). Conventional “PEGlation” methods may be used, provided that the “PEGylated” variant retains the desired function.

In another embodiment, the sustained release composition comprises a polypeptide entrapped with liposomes. Liposomes are small vehicles composed of various types of lipids, phospholipids and / or surfactants. These components are typically arranged in bilayer form, similar to the lipid arrangement of biological membranes. Liposomes containing polypeptides are described, for example, in Epstein, et al. (1985) PNAS USA 82: 3688-92, and Hwang, et al., (1980) PNAS USA, 77: 4030-34. Usually, liposomes in such preparations are of a small (about 200-800 Angstrom) monolayer type, where the lipid content is greater than about 30 mol% cholesterol, and this particular percentage is adjusted to provide optimal treatment. Useful liposomes can be produced, for example, by reverse phase evaporation using a lipid composition comprising phosphatidylcholine, cholesterol and PEG-derived phosphaditylethanolamine (PEG-PE). If desired, liposomes are extruded through filters of defined pore size to produce liposomes of a particular diameter.

The composition of the present invention may comprise a polypeptide adsorbed onto a membrane, such as a silicone membrane, which can be inserted as described in International Publication WO 91/04014.

The immunogenic compositions of the invention can be stored in standard form, including, for example, aqueous solutions or lyophilized cakes. Such compositions are typically sterilized when administered to a subject. Sterilization of the aqueous solution is readily accomplished by filtration through sterile filtration membranes. If the composition is stored in lyophilized form, the composition may be filtered before or after lyophilization and reconstitution.

2. Immunogenic Compositions Containing Polynucleotides

The present invention provides immunogenic compositions containing isolated polynucleotides encoding polypeptides of the invention. Such compositions include other components such as stock solutions such as suitable buffers such as physiological buffers. In a preferred embodiment, the other component is a pharmaceutically acceptable carrier as described above.

Alternatives to typical immunization with polypeptide antigens include direct in vivo incorporation of a polynucleotide encoding the antigen into the tissue of the subject for expression of the antigen by the tissue cell of the subject. The polynucleotide-based composition used to vaccinate a subject is referred to as a "DNA vaccine" or a "nucleic acid-based vaccine." DNA vaccines are described in International Patent Publication WO 95/20660 and International Patent Publication WO 93/19183. The ability of directly injected DNA to encode viral proteins to induce an immune response has been demonstrated through various experimental systems (Conry et al., Cancer Res., 54: 1164-1168 (1994); Cox et al., Virol, 67: 5664-5667 (1993); Davis et al., Hum.Mole.Genet., 2: 1847-1851 (1993); Sedegah et al., Proc. Natl. Acad. Sci., 91: 9866- 9870 (1994); Montgomery et al., DNA Cell Bio., 12: 777-783 (1993); Ulmer et al., Science, 259: 1745-1749 (1993); Wang et al., Proc. Natl. Acad Sci., 90: 4156-4160 (1993); Xiang et al., Virology, 199: 132-140 (1994). Studies to evaluate this technique in neutralization of influenza viruses have used both envelope and internal viral proteins to induce antibody production, with a particular focus on viral hemagglutinin protein (HA) (Fynan et al., DNA Cell. Biol., 12: 785-789 (1993A); Fynan et al., Proc. Natl. Acad. Sci., 90: 11478-11482 (1993B); Robinson et al., Vaccine, 11: 957, ( 1993); Webster et al., Vaccine, 12: 1495-1498 (1994)). Vaccination, which directly induces a protective immune response by direct influx of DNA encoding the HIV env protein, leads to both cell-mediated and humoral responses, similar to those obtained with live viruses (Raz et al. , Proc. Natl. Acad. Sci., 91: 9519-9523 (1994); Ulmer, 1993, supra; Wang, 1993, supra; Xiang, 1994, supra). In addition, reproducible immune responses to DNA encoding nuclear proteins that persist essentially over the life of the animal have been reported in mice (Yankauckas et al., DNA Cell Biol., 12: 771-776 (1993)). DNA vaccines can be designed to stimulate different cancers of the immune system. For example, histocompatibility antigen group I (MHC-I) responses are well stimulated by intracellular expression of protein antigens. To accomplish this, the sequence encoding the gp120 signal sequence is deleted and replaced with a codon for the initiator methionine residue. The gp120 gene lacking a signal sequence is synthesized on ribosomes liberated in the cytoplasm, does not result in N-linked carbohydrates, is proteolytically processed in the cell and can stimulate an MHC-I-limited immune response. The MHC-I response is believed to be particularly effective in promoting cytotoxic T cell responses mediated by CD8-containing T cells. Conversely, when the gp120 gene containing the signal sequence is expressed in mammalian cells, the signal sequence induces synthesis on membrane-bound ribosomes and is translocated into the "secretory pathway" where the cell surface or extracellular compartment Proteins scheduled to be excreted undergo a number of posttranslational modifications (eg, glycosylation) and are provided to the immune system along with major histocompatibility antigen group II (MHC-II) proteins. Protein antigens shown in connection with MHC-II antigens are particularly effective for promoting antibody responses and CD4-mediated T cell responses, but not for stimulating CD8-dependent immune responses (eg, cytotoxic T lymphocytes [ CTL]).

As is well known in the art, a number of factors can affect the expression efficiency of antigen genes and / or the immunogenicity of DNA vaccines. Examples of such factors include vectors, promoters used to induce antigen gene expression, and stability of the inserted gene in the plasmid. Promoters differ in efficiency of initiating tissue specificity and mRNA synthesis depending on their origin (Xiang et al., Virology, 209: 564-579 (1994); Chapman et al., Nucle. Acids. Res., 19: 3979). -3986 (1991)). Many mammalian vaccines in mammals have relied on viral promoters derived from cytomegalovirus (CMV). They have shown good efficiency in muscle and skin inoculation in many mammalian species.

For pharmaceutical use, the polynucleotides of the present invention are formulated in a manner suitable for a particular indication. US Patent No. 6,001,651 (Bennett et al.) Describes a number of pharmaceutical compositions suitable for use with oligonucleotide therapeutics and methods of administering such oligonucleotides. In a preferred embodiment, the therapeutic composition of the invention comprises a polynucleotide in combination with a lipid as described above.

Compositions containing polynucleotides may be stored in standard form, including, for example, aqueous solutions or lyophilized cakes. Such compositions are generally sterile when administered to cells or subjects. Sterilization of the aqueous solution is easily carried out by filtration through sterile filtration membranes. If the composition is stored in lyophilized form, the composition may be filtered before or after lyophilization and reconstitution.

3. Other Ingredients

In addition to the components described above, the immunogenic compositions of the present invention may comprise one or more adjuvants. Typical adjuvants include Freund's complete adjuvant, Freund's incomplete adjuvant, saponins, mineral gels such as aluminum hydroxide, surfactants such as lysolecithin, Pluronic polyols, polyanions, peptides, oils or hydrocarbon emulsions, keyhole limpet hemocyanin, dinitrophenols, and BCG (bacille Calmette-Guerin) and Cornebacterium parvum ), But is not limited thereto. In recent years, a new class of adjuvant, immunostimulatory oligonucleotides, has been described. They tend to be small (about 15 to 30-mer) oligonucleotides that are chemically synthesized (GC rich) containing large amounts of guanine and cytosine. In some cases (eg, particulate antigens such as hepatitis B surface antigen), these oligonucleotides may be simply mixed with viral antigens to have an immunostimulatory effect. In other cases (eg gp120), good activity is obtained by chemically binding oligonucleotides to proteins. The gp120 molecules described in this application are particularly suitable for derivatization with immunostimulatory oligonucleotides due to the unpaired cysteines that can be used to chemically bind to the oligonucleotides. The choice of adjuvant depends on the subject to be vaccinated. Preferably, pharmaceutically acceptable adjuvants are used. Preferred adjuvants for human subjects are alum (alumina gel).

Other antigens, such as other HIV-1 polypeptides (eg gp41), can be included in the immunogenic compositions of the invention.

The immunogenic composition may comprise other polypeptides that enhance or provide other advantages for the anti-gp120 immune response against the polypeptides of the invention. For example, in certain embodiments, it may be advantageous to include one or more components of the cytokine class, such as interferon or interleukin, in the immunogenic compositions of the present invention.

In a preferred embodiment, the composition containing the isolated polynucleotide of the present invention comprises a component that facilitates the introduction of the polynucleotide into the cell. Components that facilitate intracellular delivery of polynucleotides are well known and include, for example, lipids, liposomes, oil-in-water emulsions, polyethylene imines and dendrimers, which can be used in the compositions according to the invention. have. Lipids are the most widely used component of this type, and the lipids or lipid formulations that can be used can be used with the polynucleotides of the present invention. In general, cationic lipids are preferred. Preferred cationic lipids are N- [l- (2,3-dioleyloxy) propyl] -n, n, n-trimethylammoniumchloride (DOTMA), dioleyl phosphatidylethanolamine (DOPE), and / or dioleyl phosphatidylcholine (DOPC). As described for polypeptides above, polynucleotides can also be captured in liposomes.

In another embodiment, the polynucleotides form a complex with a dendrimer that can be used to transfect cells. Dendrimer polycations are three-dimensional, highly ordered oligomers typically formed on core molecules or designed initiators by repeating reaction sequences that add oligomers and / or polymers and provide a positively altered outer surface. And / or polymeric compounds. Suitable dendrimers include, but are not limited to, "starburst" dendrimers and various dendrimer polycations. Methods of making dendrimers and the use of dendrimers to introduce polynucleotides into cells in vivo are well known to those skilled in the art, see, for example, PCT / US83 / 02052 and US Pat. No. 4,507,466; 4,558,120; 4,558,120; No. 4,568,737; 4,587,329; 4,631,337; 4,694,064; No. 4,713,975; No. 4,737,550; 4,871,779; 4,857,599; And 5,661,025.

B. Use of Immunogenic Compositions

The immunogenic compositions of the invention can be used to elicit gpl20-specific immune responses in animals. The immunogenic compositions of the invention can be administered to the animal by a suitable route of administration, as described in more detail below.

In one embodiment, the immunogenic composition is administered to an animal to produce an anti-gpl20 antibody, eg, an antibody useful for HIV studies. In general, animals are those typically used for antibody production. Mammals (eg, rodents, rabbits, goats, sheep, etc.) are preferred.

Polyclonal antibodies are produced by injection (eg subcutaneous or intramuscular injection) of an antigenic polypeptide into a suitable animal (eg mouse or rabbit). The antibody is then obtained from a blood sample taken from the animal. Techniques used to generate polyclonal antibodies are described in Methods of Enzymology, "Production of Antisera With Small Doses of Immunogen: Multiple Intradermal Injections", Langone, et al. Eds. (Acad. Press, 1981). ) Are extensively described. Polyclonal antibodies produced by an animal can be further purified, for example, by binding to the matrix to which the polypeptide (an antibody is generated for this polypeptide) is bound, eluting and so on. Those skilled in the art are familiar with various standard techniques for the purification and / or enrichment of polyclonal and monoclonal antibodies (Coligan, et al. (1991) Unit 9, Current Protocols in Immunology, Wiley Interscience).

In many applications, monoclonal anti-gp120 antibodies are preferred. General methods used for the production of hybridomas that secrete mAbs are well known (Kohler and Milstein (1975) Nature, 256: 495). Briefly, as described by Kohler and Milstein, the technique isolates lymphocytes from local draining lymph nodes of five individual cancer patients, pools them, and stores the cells with SHFP-1. It was necessary to fuse. Hybridomas were screened to produce antibodies bound to cancer cell lines. Conventional screening techniques (eg, enzyme-linked immunosorbent assay, or “ELISA”) can be used to determine specificity between mAbs to determine the basic response pattern of the mAb of interest.

Alternatively, the immunogenic compositions of the present invention can be used as a vaccine for administration to a human subject. In particular, the composition can be administered to a subject not infected with HIV-1 to reduce the risk of infection or to prevent infection (prevention of HIV-1 infection). Individuals such as health professionals, police officers, and firefighters can benefit from the prophylactic administration of the vaccines of the present invention. The composition may also be administered to a subject already infected with HIV-1 but still capable of initiating an immune response (Salk, Nature 327: 473-476 (1987); Salk et al., Science 195: 834). -847 (1977)). So-called “therapeutic vaccines” provide for the improvement of existing infections (eg, by improving the subject's condition, by slowing or preventing disease progression) and / or by preventing further infection with HIV-1 strains. can do.

1. Immunogenic Compositions Containing Polypeptides

Polypeptide-based immunogenic compositions can be conveniently administered by injection (eg, subcutaneously, intradermal, intramuscular, intraperitoneal, intravenous, etc.), but delivery through catheters or other surgical tubes is also contemplated. Alternative routes include oral administration (tablets and the like) and inhalation (eg, using commercially available nebulizers for liquid formulations or lyophilization or aerosol formulations). The polypeptide composition may be administered by microspheres, liposomes, immuno-stimulating complexes (ISCOMs), or other microparticle delivery systems or sustained release formulations introduced into appropriate tissues (eg, blood).

Vaccination doses of gpl20 polypeptides administered in immunogenic compositions depend on the nature of the particular composition, eg, immunogenicity of the particular formulation, route of administration, immunization, the condition of the subject, and the like. Is within the technical level of In general, a dose of 300 μg gpl20 polypeptide per dose is most preferred, but a preferred dose may range from about 10 μg to 1 mg per dose, and doses outside this preferred range may be determined by a particular formulation, route of administration (eg, muscle Intra vs subcutaneous), and / or immunization. Different dosages may be used for successive series of inoculations. Thus, a practitioner can administer a relatively high dose at the first inoculation, followed by booster inoculation with a relatively small dose of gp120 polypeptide.

2. Immunogenic Compositions Containing Polynucleotides

The polynucleotide based immunogenic composition of the present invention can be used to express a encoded polypeptide in vivo in a subject, thereby generating an immune response against the encoded polypeptide. Benvenisty et al. (Benvenisty, N., and Reshef, L. PNAS 83, 95519555, (1986)) show that CaPO ₄ introduced into mice intraperitoneally (ip), intravenously (iv), or intramuscular (im). It was demonstrated that precipitated DNA could be expressed. Im injection of the DNA expression vector into the mouse resulted in uptake of DNA into muscle cells and expression of the protein encoded by the DNA. Plasmids were maintained in episomes and did not replicate. Subsequently, sustained expression was observed after im injection into rat, fish, and primate skeletal muscle and rat myocardium. WO 90/11092 (1990.10.4) describes the use of naked polynucleotides for vaccination of vertebrates.

Various methods can be used to introduce polynucleotides into an animal, and the selection of a suitable method for introducing a specific polynucleotide into an animal is within the skill of the art. For example, to produce anti-BGH antibodies in mice, gold microprojectiles coated with DNA encoding bovine growth hormone (BGH) were introduced into the skin of mice. Jet injectors have been used to transfect skin, muscle, fat and breast tissue of living animals. Intravenous injection of DNA: cationic liposome complexes into mice was reported by Chu et al. (Zhu et al., Science 261: 209-211 (Jul. 9,1993)) and cloned transgenes were expressed systemically. . Ulmer et al., Science 259: 1745-1749, (1993) reported on the heterologous protection of influenza virus infection by intramuscular injection of DNA encoding influenza virus proteins. WO 93/17706 describes a method of vaccinating an animal against a virus, wherein the carrier particles are coated with a gene construct and the coated particles are accelerated into the cells of the animal. "High-speed inoculation of plasmids with a gene-gun increased the immune response in mice (Fynan, 1993B, supra; Eisenbraun et al., DNA Cell Biol., 12: 791-797 (1993)). This is probably because the efficiency of DNA transfection and antigen presentation by dendritic cells is more effective The polynucleotides of the present invention may be used in other methods known in the art, for example, transfection, electroporation. , Microinjection, transduction, cell fusion, DEAE dextran, calcium phosphate sedimentation, lipofection (liposome fusion), or DNA vector transporters (Wu et al.). , J. Biol. Chem. 267: 963-967 (1992); Wu and Wu, J. Biol. Chem. 263: 14621-14624 (1988); Hartmut et al., Canadian Patent Application No. 2,012,311, 1990. 3. 15 applications).

Vaccination doses of gp120 polynucleotides administered as immunogenic compositions depend on the nature of the particular composition, eg, immunogenicity of the particular formulation, route of administration, immunization, the condition of the subject, and so on. Are within the skill of the art. Generally, a dosage of about 1 to 100 mg gpl20 polypeptide per administration is preferred. Different dosages may be used for a series of serial inoculations. Thus, the clinician may administer a relatively high dose at the first inoculation and then boost the relatively small dose of gp120 polynucleotide.

3. Immunization

The gp120 specific immune response may occur by inoculating one or more subjects with an immunogenic composition of the invention. The first inoculation is called "primary inoculation" and the subsequent inoculation is called "boost inoculation". A booster dose generally increases the immune response, and immunizations involving one or more booster doses are preferred. All types of immunogenic compositions described above can be used for primary or additional immunizations. Thus, for example, an immunogenic composition containing a polynucleotide of the invention (e.g., a virus derived vaccine) can be used for primary immunization followed by further inoculation with an immunogenic composition containing a polypeptide of the invention, The reverse is also possible. In addition, primary immunization and one or more additional immunizations may provide the same antigenic gp120 sequence and / or different antigenic gp120 sequences.

In an exemplary embodiment, suitable immunizations comprise three or more separate inoculations with one or more immunogenic compositions of the invention, wherein the second inoculation is at least about two weeks after the first inoculation, preferably from three weeks to After 8 weeks, more preferably after about 4 weeks. Generally, the third inoculation is months after the second inoculation, preferably at least about 5 months after the first inoculation, more preferably about 6 months to about 2 years after the first inoculation, even more preferably the first From about 8 months to about 1 year after inoculation. More than three periodic inoculations are desirable to increase the subject's "immune memory" (Anderson et al., J. Infectious Diseases 160 (6): 960-969 (Dec. 1989)).

The suitability of the selected immunization parameters, such as formulation, dose, inoculation, etc., can be determined by assaying antibody titers during the course of the immunization program by aliquoting serum from the subject. Alternatively, the T cell population can be monitored by conventional methods. In addition, subjects may be tested for the desired effect, such as prevention of HIV-1 infection or progression to AIDS, improvement of disease state (e.g., reduction of viral load), or reduction of transmission frequency to an uninfected partner. Monitor the clinical condition of the If such monitoring indicates that vaccination is not optimal, the subject may be boosted with additional doses of the immunogenic composition, and the vaccination parameters may be changed in a way that is expected to enhance the immune response. Thus, for example, the dose of a gp120 polypeptide or polynucleotide and / or adjuvant may be increased, the gp120 polypeptide may bind to or form a complex with an immunogenic carrier protein, or the route of administration may be altered.

Diagnostic method

A. Detection of Antibodies Specific to gp120 Polypeptides with Abnormal Disulfide Structures

The present invention provides a diagnostic method for determining whether a subject produced an antibody specific for GP120 of the present invention. This method requires contacting a biological sample obtained from a subject with a GP120 polypeptide of interest and determining whether the sample contains an antibody that specifically binds to the GP120 polypeptide. The sample used may comprise any tissue containing the antibody, but the most convenient is the blood or blood fraction (eg serum or plasma).

Anti-GP120 antibodies can be detected and / or quantified in a sample using a number of known immunoassays (see US Pat. Nos. 4,366,241; 4,376,110; 4,517,288; and 4,837,168). For a general overview of immunoassays, see Cell Biology Volume 37: Antibodies in Cell Biology, Asai, ed.Academic Press, Inc. New York (1993); Basic and Clinical Immunology 7th Edition, Stites & Terr, eds. 1991).

In standard solid phase format, one can attach the gp120 polypeptide of interest to a solid phase that acts as a capture agent to immobilize antibodies in a sample specific for the gp120 polypeptide. The bound antibody can then be separated from the free antibody in the sample by a simple washing step.

Immunoassays typically use a labeling reagent that specifically binds and labels a gp120 polypeptide and a binding complex formed by an antibody in a sample specific for the gp120 polypeptide. Any suitable labeling system, direct or indirect, can be used. For example, labeled antibodies specific for the species of the subject under test can be used to label antibodies bound to a solid phase. Other polypeptides that can specifically bind immunoglobulin constant regions, such as polypeptide A or polypeptide G, can also be used as labeling reagents. Such polypeptides are a common component of the cell wall of streptococci. They exhibit strong non-immunogen reactivity with immunoglobulin constant regions from various species (Kronval, et al. (1973) J. Immunol., 111: 1401-1406, and Akerstrom (1985) J. Immunol., 135: 2589-2542). Suitable labels include those discussed above with respect to labeling the gp120 polypeptide of the invention.

Assays of the invention are recorded according to standard methods well known in the art (as positive or negative, or as quantities of anti-gp120 antibodies). The specific recording method depends on the assay format and the choice of label. For example, Western blot assays can be recorded by visualizing the colored product produced by enzyme labeling. The presence of colored bands or spots clearly visible at the correct molecular weight is recorded as a positive result, while the absence of clearly visible spots or bands is recorded negative. The intensity of the band or spot provides a quantitative measure of the anti-gp120 antibody concentration.

In a preferred embodiment, the immunoassay according to the invention is carried out using a MicroElectroMechanical System (MEMS). MEMS are microscopic structures integrated on silicon that combine mechanical, optical, and fluid elements with electronics to enable convenient detection of analytes of interest. An exemplary MEMS device suitable for use with the present invention is a Protiveris' multicantilever array. This array is based on the chemical-mechanical actuation of specially designed silicon microcantilevers and the optical detection of subsequent microcantilever deflections. When a microcantilever coated on one side with a protein, antibody, antigen or DNA fragment is exposed to a solution containing complementary molecules, the microcantilever bends. This bending is due to the change in surface energy due to the binding event. Optical detection of the degree of bending (deflection) allows measuring the amount of complementary molecules bound to the microcantilever.

B. Detection of gp120 Sequences with Abnormal Disulfide Structures

The invention also provides whether a biological sample obtained from a subject contains a polypeptide comprising a gp120 amino acid sequence characterized by an abnormal disulfide structure and / or a polynucleotide encoding a gp120 amino acid sequence characterized by an abnormal disulfide structure. It provides a diagnostic method for determining. Abnormal disulfide structure may represent a "transmission phenotype" associated with a new major strain or HIV infection spreading in North America. This method requires assaying a sample for a polypeptide comprising the gp120 sequence or a polynucleotide encoding the gp120 sequence, wherein the gp120 sequence is numbered from the N-terminal methionine of gp120 from the HXB-2 strain of HIV gp120 (a) at least one cysteine residue at one or more of positions 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, 331, 378, 385, 418, and 445 And / or (b) 24, 29, 34, 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, 331, 378, 385, 418, 445 One or more additional cysteine residues at positions other than 493, 495, 499-501, 503-508, and 510. In a preferred embodiment, the gp120 sequence is not a subtype G gp120 sequence having one or more additional cysteines in the V1 domain or a subtype E gp120 sequence having one or more additional cysteines in the V4 domain. The diagnostic method of the present invention utilizes an assay capable of detecting the presence of a polypeptide comprising a gp120 sequence having an abnormal disulfide structure and / or a polynucleotide encoding a gp120 sequence having an abnormal disulfide structure and optionally quantifying Can be performed. The sample used can comprise a polypeptide comprising a gp120 amino acid sequence or a tissue that is expected to contain a polynucleotide encoding the gp120 amino acid sequence. Conveniently, blood or blood fractions (eg serum or plasma) are sampled for the assay.

1. gpl20 polypeptide-based assay

Immunoassays are generally most convenient for the detection of gp120 polypeptides characterized by abnormal disulfide structures. Considerations for performing an immunoassay for detecting a gp120 polypeptide, e.g., format, labeling system, are described substantially above with respect to the detection of anti-gp120 antibodies.

Preferred immunoassays for detecting gp120 polypeptide are competitive or noncompetitive assays. Noncompetitive immunoassays are assays in which the amount of gp120 polypeptide bound to a specific antibody is directly measured. In a competitive assay, the amount of gp120 polypeptide in a sample is determined indirectly by measuring the amount of added (exogenous) polypeptide that is substituted from (or competed with) the specific antibody.

Antibodies useful for such immunoassays include polyclonal and monoclonal antibodies, which may be generated, for example, as described above.

2. gp120 polynucleotide based assay

A gp120 polynucleotide encoding a gp120 sequence characterized by an abnormal disulfide structure is generally detected based on specific hybridization of a suitable nucleic acid molecule to a sample polynucleotide. The nucleic acid molecule specifically hybridizes with a target nucleotide sequence that is present in the gp120 polynucleotide to be detected in the sample nucleotide and not in the other nucleotide. In a preferred embodiment, the nucleic acid molecule is substantially complementary to the target nucleotide sequence.

Polynucleotides can be prepared from samples according to one of many methods well known in the art. General methods for isolation and purification of polynucleotides are described in Tijssen ed., (1993) Chapter 3 of Laboratory Techniques in Biochemistry and Molecular Biology: Hybridization With Nucleic Acid Probes, Part L Theory and Nucleic Acid Preparation, Elsevier, NY and Tijssen ed This is explained in detail in. In a preferred embodiment, the gp120 polynucleotide can be amplified after it is obtained by reverse transcription from a sample containing HIV-1 viral RNA.

i. Amplification test

In one embodiment, an amplification assay can be used to detect and optionally quantify a gp120 polypeptide of interest. In this amplification assay, the gp120 polynucleotide in the sample acts as a template in an amplification reaction performed using nucleic acid primers containing a detectable label or component of a labeling system. Suitable amplification methods include polymerase chain reaction (PCR), reverse transcription PCR (RT-PCR); Ligase chain reaction (LCR) (Wu and Wallace (1989) Genomics 4: 560, Landegren et al. (1988) Science 241: 1077, and Barringer et al. (1990) Gene 89: 117); Transcription amplification (Kwoh et al. (1989) Proc. Natl. Acad. Sci. USA 86: 1173), self-sustained sequence replication (Guatelli et al. (1990) Proc. Nat. Acad. Sci. USA 87: 1874; Dot PCR, linker adapter PCR, and the like.

If it is desired to determine the level of gp120 polynucleotides, a number of well known "quantitative" amplification methods can be used. Quantitative PCR generally involves co-amplifying a known amount of control sequence simultaneously using the same primers. This provides an internal standard that can be used to calibrate the PCR reaction. Detailed protocols for quantitative PCR are provided in PCR Protocols, A Guide to Methods and Applications, Innis et al., Academic Press, Inc. N. Y., (1990).

ii. Hybridization System Test

Nucleic acid hybridization simply involves contacting a nucleic acid probe with a sample polynucleotide under conditions such that the probe and its complementary target nucleotide sequence can form a stable hybrid duplex through complementary base pairing. Nucleic acid that does not form a hybrid duplex is then detected through detection of a component of a detectable label or labeling system that is washed off and remains attached to the hybridized nucleic acid. Methods of detecting and / or quantifying polynucleotides using nucleic acid hybridization techniques are known to those skilled in the art (Sambrook et al. Supra). Hybridization techniques are described in Hames and Higgins (1985) Nucleic Acid Hybridization, A Practical Approach, IRL Press; Gall and Pardue (1969) Proc. Natl. Acad. Sci. USA 63: 378-383; John et al. (1969). Nature 223: 582-587). Methods for optimizing hybridization conditions are described in Tijssen (1993) Laboratory Techniques in Biochemistry and Molecular Biology, Vol. 24: Hybridization With Nucleic Acid Probes, Elsevier, N. Y.

The nucleic acid probes used herein for the detection of gp120 polynucleotides may be less than or less than the full length of these polynucleotides. Shorter probes are generally tested empirically for specificity. Preferably, the nucleic acid probe is at least about 15 bases, more preferably at least about 20 bases in length. See Sambrook et al. For how to select nucleic acid probe sequences for use in nucleic acid hybridization. Visualization of the hybridized probes enables quantitative determination of the presence or absence of the gp120 polynucleotide of interest, and standard methods (eg, density methods in which nucleic acid probes are radioactively labeled) quantify the level of gp120 polynucleotides. Can be used to

 Various additional nucleic acid hybridization formats are known to those skilled in the art. Standard formats include sandwich assays and competition or substitution assays. Sandwich assays are commercially useful hybridization assays that detect or isolate polynucleotides. This assay utilizes "capture" nucleic acids covalently immobilized on a solid support and labeled "signal" nucleic acids in solution. The sample provides a target polynucleotide. Capture nucleic acids and signal nucleic acids each hybridize with a target nucleotide to form a "sandwich" hybridization complex.

In one embodiment, the method of the present invention can be used in an array based hybridization format. In an array format, many different hybridization reactions can occur substantially "in parallel". This provides a quick and practical simultaneous evaluation of many hybridizations in one experiment. Methods of performing hybridization reactions in array based formats are well known to those skilled in the art. See Pastinen (1997) Genome Res. 7: 606-614; Jackson (1996) Nature Biotechnology 14: 1685; Chee (1995) Science 274: 610, WO 96/17958, Pinkel et al. (1998) Nature Genetics 20: 207-211).

Arrays, particularly nucleic acid arrays, can be produced according to a variety of methods well known to those skilled in the art. For example, in a simple embodiment, a “low density” array is simply made by spotting different nucleic acids at different locations on a solid support (eg, glass surface, membrane, etc.) (eg by hand using a pipette). Can be generated. This simple spotting method was automated to produce a high density spotted microarray. For example, US Pat. No. 5,807,522 describes the use of an automated system that taps microcapillaries against a surface to deposit a small volume of biological sample. This process is repeated to create a high density array. Arrays can also be generated using oligonucleotide synthesis techniques. Thus, for example, US Pat. Nos. 5,807,522 and PCT Patent Publications 90/15070 and 92/10092 teach the use of light-directed combinatorial synthesis of high density oligonucleotide arrays. Synthesis of high density arrays is described in US Pat. No. 5,744,305; 5,800,992; 5,800,992; And 5,445,934.

In a preferred embodiment, the array used in the present invention contains a "probe" nucleic acid. These probes then each hybridize with the target nucleotide sequence present in the polynucleotide obtained from the biological sample. Alternatively, polynucleotides from different samples can be arrayed and then reformatted such that the array is probed with one or more probes that can be distinguishably labeled.

Many methods for immobilizing nucleic acids on various solid surfaces are known in the art. A wide range of organic and inorganic polymers and other materials can be used as materials for solid surfaces, both natural and synthetic. Exemplary solid surfaces include, for example, nitrocellulose, nylon, glass, quartz, diazotized membranes (paper or nylon), silicon, polyformaldehyde, cellulose, and cellulose acetate. In addition, plastics such as polyethylene, polypropylene, polystyrene and the like can be used. Other materials that can be used include paper, ceramics, metals, metalloids, semiconductor materials, and the like. In addition, materials that form gels can be used. Such materials include, for example, proteins (eg gelatin), lipopolysaccharides, silicates, agarose and polyacrylamides. If the solid surface is porous, various pore sizes may be used depending on the nature of the system.

In surface preparation, many different materials can be used, in particular, as laminates in order to obtain a variety of properties. For example, a protein (eg bovine serum albumin) or a mixture of macromolecules (eg denhardt solution) may be used to avoid nonspecific binding, simplify covalent conjugation and / or increase signal detection. Can be. If a covalent bond between the compound and the surface is desired, the surface may be multifunctional or polyfunctionalized. Functional groups present on the surface and which may be used for bonding may include carboxylic acids, aldehydes, amino groups, cyano groups, ethylene groups, hydroxyl groups, mercapto groups and the like. The manner in which the various compounds are bound to the various surfaces is well known and fully exemplified in the literature.

The array may consist of target elements of various sizes from about 1 mm in diameter to as small as about 1 μm. A relatively simple method of quantitatively fluorescence imaging of 1 cm 2 area has been described that allows acquisition of data from multiple target elements in one image (see Wittrup (1994) Cytometry 16: 206-213, Pinkel et. al. (1998) Nature Genetics 20: 207-211.

Hybridization assays according to the present invention can be performed using a MicroElectroMechanical System (MEMS), such as a Protiveris' multicantilever array.

iii. Detection of gp120 Polynucleotides

gp120 polynucleotides are detected by labels detectable with the polynucleotide-based assay. The labels discussed above can be used in the polynucleotide based assays of the present invention. The label can be added to the probe or primer or sample polynucleotide before or after hybridization or amplification. So-called "direct labels" are detectable labels that are directly attached or incorporated into the labeled polynucleotides prior to performing the assay. In contrast, the so-called "indirect label" binds to the hybrid duplex after hybridization. For indirect labels, one of the polynucleotides in the hybrid duplex carries the component to which the detectable label binds. Thus, for example, the probe or primer may be biotinylated prior to hybridization. After hybridization, the avidin conjugated fluorophore is combined with the biotin bearing hybrid duplex to provide a label that is easily detected. For a detailed overview of methods for labeling and detecting polynucleotides, see Laboratory Techniques in Biochemistry and Molecular Biology, Vol. 24: Hybridization With Nucleic Acid Probes, P. Tijssen, ed.Elsevier, NY, (1993). Reference may be made.

The sensitivity of the hybridization assay can be increased using a polynucleotide amplification system that increases the target polynucleotide detected. Examples of such systems include polymerase chain reaction (PCR) systems and ligase chain reaction (LCR) systems. Other methods recently described in the prior art are nucleic acid sequence based amplification (NASBAO, Cangene, Mississauga, Ontario) and Q Beta Replicase systems.

In a preferred embodiment suitable for use in the amplification assay of the present invention, the primer contains two fluorescent dyes "reporter dye" and "quencher dye. If undamaged, the primer is quencher. Very low fluorescence levels due to the dye effect: if the primer cleaves or degrades (e.g., by the exonuclease activity of the polymerase, see below), the reporter dye will fluoresce and by a suitable fluorescence detection system Amplification by many techniques (PCR, RT-PCR, RCA, or other amplification methods) can be accomplished using suitable DNA polymerases (eg, Taq DNA polymerase) with polymerase and exonuclease activity. This polymerase increases the fluorescence as a result of synthesizing new DNA strands and, in the process, digesting the labeled primers. Commercially available fluorescence detection systems are ABI Prism® Systems 7000, 7300, 7500, 7700, or 7900 (TaqMand3) or Roche's LightCycler® System from Applied Biosystems. ).

The following examples are provided for purposes of illustration and are not intended to limit the invention.

Example

Example 1

Expression of the gp120 Polypeptide

The HIV-1 gp120 sequence is preferably expressed as a fusion protein containing a heterologous signal sequence and an epitope tag. Exemplary preferred signal sequences include those obtained from herpes simplex virus-1 (HSV1) gD glycoprotein and human tissue plasminogen activator (tPA). The first 29 amino acids of mature HSV1 gD act as epitope tags, which bind to residue 42 of HIV gp120 when numbered from the N-terminal methionine (residue 12 of mature gp120) of the HXB2 strain of gp120.

pCI.gD.gpl20 contains the mammalian transcriptional unit and the pUC vector backbone (pCI mammalian expression vector available from Promega Corporation, Madison WI). The transcription unit comprises the cytomegalovirus (CMV) immediate early promoter and artificial intron followed by the first 29 amino acids of the mature HSV1 gD glycoprotein fused to residue 42 of HIV-1 gp120 at the signal sequence and KpnI site. Contains the coding region. The gpl20 sequence ends at the stop codon and the XhoI restriction site as mentioned above. Within the vector is followed by the SV40 poly-A sequence and the electron terminator.

pCI.tPA.gp120 also contains a mammalian transcriptional unit and a pUC vector backbone (pCI mammalian expression vector available from Promega Corporation, Madison WI). The transcription unit comprises a cytomegalovirus (CMV) early early promoter and an artificial intron followed by the first 36 amino acids of the tPA pre-pro sequence and a mature HSV1 gD glycoprotein fused to residue 42 of HIV-1 gp120 at the KpnI site. Contains the coding region for the first 29 amino acids. The gpl20 sequence ends at the stop codon and the XhoI restriction site as mentioned above. Within the vector is followed by the SV40 poly-A sequence and the electron terminator.

The sequence encoding the gp120 polypeptide of the invention was amplified by polymerase chain reaction (PCR) to generate a DNA fragment extending from amino acid residues 42 to amino acid residues 529. The fragment has a KpnI restriction site at the 5 'end and a stop codon followed by an XhoI restriction site at the 3' end. Such restriction sites facilitate cloning into the pCI.gD.gp120 vector or pCI.tPA.gpl20 vector.

The gpl20 amplification product was digested with KpnI and XhoI restriction enzymes, and 1.5 kb gpl20 fragments were isolated using commercially available kits such as the QIAquick PCR Purification Kit (Qiagen, Valencia, Calif.). PCI.gD.gpl20 or pCI.tPA.gpl20 were digested with KpnI and XhoI and 4.3 kb vector fragments were isolated by commercially available kits such as the QIAquick gel extraction kit (Qiagen, Valencia, CA). gp120 fragment was ligated into either vector. Ligation products were transformed into ToplO E. coli. DNA was prepared, digested with KpnI and XhoI and subjected to gel electrophoresis to confirm that the transformants contained the desired construct. Gene expression was then determined using a calcium phosphate technique (Graham et al., Virology 52: 456-467 (1973)) using the 293T embryonic human kidney cell line (Graham et al., J. Gen. Virol. 36: 59- 77 (1977) were transiently transfected and subsequently tested by assaying medium conditioned by Western blot using polyclonal rabbit anti-gp120 antiserum.

Example 2

Virus infectivity and neutralization assay

Since in vitro culture of HIV-1 inevitably imposes selective conditions, accurate presentation of the circulating virus in HIV-1 infected patients is an intermediate test from material derived from the patient (eg, plasma, white blood cells, brain). It can only be obtained by examining viral sequences that are molecularly cloned without an in vitro culture step. The cloned complementary DNA (cDNA) obtained from the retroviral RNA genome can then be inserted into a stable DNA based expression system for further analysis. One such expression system is the PhenoSense ^™ HIV neutralization assay (as described in detail in Richman et al., 2003). In brief, the assay creates a pseudotype virus that expresses a cloned HIV-1 envelope protein and then uses the virus for viral infectivity studies. This assay has been used to determine the phenotype of cloned HIV envelope glycoproteins with respect to chemokine receptor use (CXCR4 or CCR5) and susceptibility and viral neutralizing antibodies to soluble CD4. This assay has been shown to correlate with conventional virus neutralization assays in which the ability of antibodies to inhibit activated peripheral blood monocytes (PBMCs) is measured.

PhenoSense ^™ assays have advantages over conventional methods in that they are faster, more sensitive, and use limited viruses. This avoids potential artifacts resulting from virus selection in vitro. The PhenoSense ^™ assay uses nucleic acid amplification (RT-PCR) to obtain an HIV envelope sequence (gp160) from HIV-positive patient plasma samples. The amplified envelope sequences are inserted into expression vectors (pCXAS) using conventional cloning methods. Expression vectors can be prepared from single isolated molecular clones or from large pools of sequences that accurately represent various virus like species in the patient at the time of sample collection. Recombinant HIV-1 stocks expressing viral envelope proteins (pooled gp160 or individual gp160), HEK293 cells, a defective HIV-1 genomic viral vector lacking HIV-1 envelope protein and the HIV envelope protein of interest The second expression vector is prepared by cotransfection. The HIV-1 genomic vector is replication defective and contains a luciferase expression cassette in the deleted region of the HIV envelope gene. Pseudotype recombinant virus with patient virus envelope protein, and CXCR4 and CCR5 dependent control virus (NL4-3, JRCSF) and specific control murine leukemia virus (A-MLV) were collected 48 hours post-transfection and 37 Incubate with serial monoclonal antibodies and / or plasma control 4-fold dilutions for 1 hour at < RTI ID = 0.0 > U87 cells expressing CD4 / CCR5 and cells expressing CD4 / CXCR4 were inoculated with virus-antibody dilutions. Viral infectivity was determined by measuring the amount of luciferase activity expressed in infected cells 72 hours after inoculation and recorded as Balanced Relative Light Units (RLUs). Neutralizing activity was expressed as the rate of inhibition of viral replication (luciferase activity) at each antibody concentration compared to the antibody negative control. IC50 is defined as the concentration of monoclonal antibody required to inhibit 50% viral infectivity. Viruses were classified as susceptible to neutralization when the IC50 was at least three times higher than the IC50 of the same reagent for the specific control virus A-MLV.

Experiment result

Three U-099 (having 19 cysteine residues), U-209 (having 19 cysteine residues) and U-210 (having 20 cysteine residues) of the cysteine mutants were subjected to the PhenoSense ^™ infectivity and neutralization assay And the results are shown in Table 2. Each virus binds to and infects U87 cells expressing CD4 and CCR5 chemokine receptors, but not to U87 cells expressing CD4 and CXCR4 co-receptors, indicating that these mutant viruses are only R5 phenotype. Virus was differentially neutralized using monoclonal antibodies (MAbs) targeting gp41 (4E10 and 2F5) and gpl20 (2G12). 19-cysteine mutant U-099 showed 2-8 times more resistance to gp41 MAbs, but neutralized by the extent of other mutants using gpl20 MAb 2G12. Interestingly, U-210 was not neutralized by 2G12, a MAb that is thought to exhibit extensive cross-neutralization for primary HIV isolates (see Trkola et al., 1996). However, since 2G12 binding is susceptible to mutations in V4 and U-210 has two additional cysteine residues in this region, neutralization failure can be mediated by these cysteine mutations. The results of this study demonstrate that HIV isolates processing 19 and 20 cysteine residues rather than the typical 18 cysteine residues are functional and can mediate infection of cells containing CD4 and CCR5 chemokine receptors. .

TABLE 2

IC50 is defined as the concentration of monoclonal antibody required to inhibit 50% viral infectivity. MAbs 4E10 and 2F5 target the region at gp41, while MAb 2G12 recognizes the epitope at gpl20. 92HT594 is a dual-tropic virus control. JRCSF and NL43 are controls for R5 and X4 chemotaxis, respectively. A-MLV is a non-HIV virus that infects either cell type (R5 or X4) but is not inhibited by HIV MAbs. NA; Not applicable.

references

Richman DD, Wrin T, Little SJ, Petropoulos CJ. (2003). Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proceedings of the National Academy of Sciences U S A. 100 (7): 4144-4149.

2. Trkola A, Purtscher M, Muster T, Ballaun C, Buchacher A, Sullivan N, Srinivasan K, Sodroski J, Moore JP, and Katinger H. (1996). Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gpl20 glycoprotein of Human Immunodeficiency Virus Type 1. Journal of Virology 70 (2): 1100-1108.

All publications and patents mentioned in this specification are herein incorporated by reference to the same extent as if each publication or patent was specifically and individually indicated to be incorporated by reference.

                         SEQUENCE LISTING <110> VaxGen, Inc.        Berman, Phillip W        Jobes, David V   <120> HIV-1 ENVELOPE GLYCOPROTEINS HAVING UNUSUAL DISULFIDE STRUCTURE <130> 409J-000210US / PC <140> US 10 / 866,527 and PCT / US 04/018672 <141> 2004-06-10 <160> 140 <170> PatentIn version 3.2 <210> 1 <211> 1613 <212> DNA <213> Human immunodeficiency virus type 1 <400> 1 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaggaat tgtcagcgct 60 ggtggagatg gggcatcatg ctccttggaa tgttgatgat ctgtaatgct gtaggacaat 120 tgtgggttac ggtctattat ggggtacctg tgtggaaaga agccaccacc actctattcc 180 gtgcatcaga tgctaaagca tatgatacag aggtacataa tgtctgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaaa tagaattgga aaatgtgaca gaaactttta 300 acatgtggaa aaataacatg gtagaacaaa tgcatgagga tataatcagt ttatgggatc 360 aaggcctaaa accatgtgta aaattaaccc cactccgtgt tactttaaat tgcactgact 420 acaagaatgc taatagtacc aataataata gtaccagtga tagtagcaat ctagaagagg 480 agaaaggaga aataaaaaac tgctctttca atatcactac aagcataaaa gataggatgc 540 agaaagaata tgcacttttt tataaacttg atatagtacc aatagataat aataatacta 600 gatataggat gataagttgt aacacctcag tcattacaca ggcctgtcca aaggtatctt 660 ttgagccaat tcccatacat tattgtgccc cggctggttt tgcgattcta aaatgtaagg 720 ataagaagtt caatggaaca ggaccatgta gaaatgtcag cacagtacaa tgtacacatg 780 gaattaggcc agtagtatca actcaattgc tgttaaatgg cagtctagca gaagaagagg 840 tagtacttag atctgaaaat ttcacgaaca atgctaaaac cataatagta cagctaaaag 900 aacctataaa aatcaattgt acaagaccca acaacaatac aagaaaaagt atacatatag 960 gaccagggag agcattttat acaacagggg agataatagg agacataaga caagcacatt 1020 gtagcattag taaggtagaa tggaacaaca ctttgataca aatagttgaa aaattaagag 1080 aacaatttgg gactaaaaca ataaatttta ctaaaccctc aggaggggac ctagaaattg 1140 taacgcacag ctttaattgt agaggggaat ttttctactg taataccaca aaactgttta 1200 atagtacttg gcctgggaat attacttgga ctcggaataa taatgttact acagaaaata 1260 tcacactccc atgcagaata aaacaaattg tgaacagatg gcaggaagta ggaaaagcaa 1320 tgtatgcccc tcccatccaa ggacaaatta gatgttcatc aaatattaca gggctgctat 1380 taacaagaga tggtggtggg gaccagaata gcacagggga gatcttcaga cctggaggag 1440 gagatatgag ggacaattgg agaagtgaac tatacaaata taaagtagta caaattgaac 1500 cattaggaat agcacccacc aaggcaagga gaagagtggt gcagagagaa aaaagagcag 1560 tgggaacatt aggagctatg ttccttgggt tcttgggagc agcaggaagc act 1613 <210> 2 <211> 484 <212> PRT <213> Human immunodeficiency virus type 1 <400> 2 Asn Ala Val Gly Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Arg Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Ile Glu Leu Glu Asn Val Thr Glu Thr     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Gly Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Arg Val Thr Leu Asn Cys Thr Asp Tyr Lys Asn Ala Asn Ser Thr             100 105 110 Asn Asn Asn Ser Thr Ser Asp Ser Ser Asn Leu Glu Glu Glu Lys Gly         115 120 125 Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Ser Ile Lys Asp Arg     130 135 140 Met Gln Lys Glu Tyr Ala Leu Phe Tyr Lys Leu Asp Ile Val Pro Ile 145 150 155 160 Asp Asn Asn Asn Thr Arg Tyr Arg Met Ile Ser Cys Asn Thr Ser Val                 165 170 175 Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His             180 185 190 Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Lys Asp Lys Lys         195 200 205 Phe Asn Gly Thr Gly Pro Cys Arg Asn Val Ser Thr Val Gln Cys Thr     210 215 220 His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser 225 230 235 240 Leu Ala Glu Glu Glu Val Val Leu Arg Ser Glu Asn Phe Thr Asn Asn                 245 250 255 Ala Lys Thr Ile Ile Val Gln Leu Lys Glu Pro Ile Lys Ile Asn Cys             260 265 270 Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile His Ile Gly Pro Gly         275 280 285 Arg Ala Phe Tyr Thr Thr Gly Glu Ile Ile Gly Asp Ile Arg Gln Ala     290 295 300 His Cys Ser Ile Ser Lys Val Glu Trp Asn Asn Thr Leu Ile Gln Ile 305 310 315 320 Val Glu Lys Leu Arg Glu Gln Phe Gly Thr Lys Thr Ile Asn Phe Thr                 325 330 335 Lys Pro Ser Gly Gly Asp Leu Glu Ile Val Thr His Ser Phe Asn Cys             340 345 350 Arg Gly Glu Phe Phe Tyr Cys Asn Thr Thr Lys Leu Phe Asn Ser Thr         355 360 365 Trp Pro Gly Asn Ile Thr Trp Thr Arg Asn Asn Asn Val Thr Thr Glu     370 375 380 Asn Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Val Asn Arg Trp Gln 385 390 395 400 Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Gln Gly Gln Ile Arg                 405 410 415 Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Gly             420 425 430 Asp Gln Asn Ser Thr Gly Glu Ile Phe Arg Pro Gly Gly Gly Asp Met         435 440 445 Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Gln Ile     450 455 460 Glu Pro Leu Gly Ile Ala Pro Thr Lys Ala Arg Arg Arg Val Val Gln 465 470 475 480 Arg Glu Lys Arg                  <210> 3 <211> 1604 <212> DNA <213> Human immunodeficiency virus type 1 <400> 3 agaaagagca gaagacagtg gcaatgaaag tgacggggat caggaagaat tgtcagcgct 60 tgtggagatg gggcatgatg ctcctgggga tgttaatgat ctgtagtgct gcagaacaat 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga agcaaccacc actctatttt 180 gtgcatcaga tgctaaagca tatgacgcag agaaacataa tgtttgggcc acacatgcct 240 gcgtacccac agaccccaac ccacaagaaa tagtattgga aaatgtgaca gaatatttta 300 atgcttggaa aaataacatg gtagaacaga tgcatgagga tataatcagt ttatgggatc 360 aaagcctaaa accatgtgta aaattaaccc cactctgtgt tactttaaat cgcactgatt 420 tgaataatag tactaacacc actaatagta atagcagcgg ggggatgatg agagaagaaa 480 tgaaaaactg ctctttcaat atcaccacaa caataggtga taggaggcaa aaagaatatg 540 cactttttta taaacttgat atagcatcaa taaaggatga tgctaataat ttcacatata 600 ggttgataag ttgtaacacc tcagtcatta cacaagcctg tccaaagata tcctttgagc 660 caattcccat acattattgt gccccggctg gttttgcaat tctaaagtat aacgataaga 720 agttcaatgg agaagagcaa tgtaaaaatg tcagcacagt acaatgtaca catggaatta 780 agccagtagt atcaactcag ctgctgttaa atggtagtct agcagaagaa gagatagtaa 840 ttagatctga caatttcaca gacaatgcta aaaccataac agtacagctg aatgaatctg 900 tagtaattaa ttgtacaaga ccccacaaca atacaagaaa aagtataaat ataggaccag 960 ggagagcatg gtatacaaca ggagaaataa taggagatat aagacaagca cattgtaaca 1020 ttagtaaaac acaatggaat aacactttaa taaagatagt taaaaaatta agagaacaat 1080 ttaatacaaa caccataatc tttaatcaat ccacaggagg ggacctagaa attgtaatgc 1140 acagttttaa ttgtggaggg gaatttttct actgtgatac aacacaactg tttaatagta 1200 cttggaatat tactggagaa agtacttgga atagtactgg aaaaacaaat gaaactatca 1260 cactcccatg tagaataaaa caagttataa acatgtggca gcaagtaggg aaagcaatgt 1320 atgcccctcc catcaaaggg caaattagat gttcatcaaa tattacaggg ctgctattaa 1380 caagagatgg tggtaagaac agcagtaacg ggactgagac ctttagacct ggaggaggag 1440 atatgaggga caattggaga agtgaattat ataaatataa agtagtagaa attgaaccat 1500 taggaatagc acccactaag gcaaagagaa gagtggtgca gagagaaaga agagcagtaa 1560 taggagctat gttccttggg ttcttgggag cagcaggaag cact 1604 <210> 4 <211> 483 <212> PRT <213> Human immunodeficiency virus type 1 <400> 4 Ser Ala Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Ala Glu Lys His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Ile Val Leu Glu Asn Val Thr Glu Tyr     50 55 60 Phe Asn Ala Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Arg Thr Asp Leu Asn Asn Ser Thr Asn Thr             100 105 110 Thr Asn Ser Asn Ser Ser Gly Gly Met Met Arg Glu Glu Met Lys Asn         115 120 125 Cys Ser Phe Asn Ile Thr Thr Thr Ile Gly Asp Arg Arg Gln Lys Glu     130 135 140 Tyr Ala Leu Phe Tyr Lys Leu Asp Ile Ala Ser Ile Lys Asp Asp Ala 145 150 155 160 Asn Asn Phe Thr Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val Ile Thr                 165 170 175 Gln Ala Cys Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile His Tyr Cys             180 185 190 Ala Pro Ala Gly Phe Ala Ile Leu Lys Tyr Asn Asp Lys Lys Phe Asn         195 200 205 Gly Glu Glu Gln Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly     210 215 220 Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala 225 230 235 240 Glu Glu Glu Ile Val Ile Arg Ser Asp Asn Phe Thr Asp Asn Ala Lys                 245 250 255 Thr Ile Thr Val Gln Leu Asn Glu Ser Val Val Ile Asn Cys Thr Arg             260 265 270 Pro His Asn Asn Thr Arg Lys Ser Ile Asn Ile Gly Pro Gly Arg Ala         275 280 285 Trp Tyr Thr Thr Gly Glu Ile Ile Gly Asp Ile Arg Gln Ala His Cys     290 295 300 Asn Ile Ser Lys Thr Gln Trp Asn Asn Thr Leu Ile Lys Ile Val Lys 305 310 315 320 Lys Leu Arg Glu Gln Phe Asn Thr Asn Thr Ile Ile Phe Asn Gln Ser                 325 330 335 Thr Gly Gly Asp Leu Glu Ile Val Met His Ser Phe Asn Cys Gly Gly             340 345 350 Glu Phe Phe Tyr Cys Asp Thr Thr Gln Leu Phe Asn Ser Thr Trp Asn         355 360 365 Ile Thr Gly Glu Ser Thr Trp Asn Ser Thr Gly Lys Thr Asn Glu Thr     370 375 380 Ile Thr Leu Pro Cys Arg Ile Lys Gln Val Ile Asn Met Trp Gln Gln 385 390 395 400 Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Lys Gly Gln Ile Arg Cys                 405 410 415 Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Lys Asn             420 425 430 Ser Ser Asn Gly Thr Glu Thr Phe Arg Pro Gly Gly Gly Asp Met Arg         435 440 445 Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Glu Ile Glu     450 455 460 Pro Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg 465 470 475 480 Glu arg arg              <210> 5 <211> 1613 <212> DNA <213> Human immunodeficiency virus type 1 <400> 5 agaaagagca gaagacagtg gcaatgagag tgatggggat gaggaagaat tatcagcact 60 ggtggagagg gggcatcttg ctccttggga tgttaatgat cagtagtgct atagaaaatt 120 cgtgggtcac agtctattat ggggtacctg tgtggaaaga agctaccacc actttatttt 180 gtgcatcaga tgctaaagct tatgaaacag aggcacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaaa taaaattgga aaatgtgtca gaaaatttta 300 acatgtggaa aaataacatg gtagaccaaa tgcatgagga tataatcagt ttatgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cactctgtgt tactttaaat tgcactgatt 420 attttgggaa tactactaat accaatacta ataccaccag tagtcccagc accaacagta 480 gtaatgaagg agaagtgaaa aaatgctctt tcaatatcac cacagaagta agggacaagg 540 tgcgaaaaga atttgcactt ttttataaac ttgatatagt acgaacaggt catgataata 600 ctagctatag gttgataagt tgtaacacct cagtcattac acaggcctgc ccaaagatat 660 cctttgatcc aattcccata cattattgtg ccccggctgg ttttgcgatt ctcaagtgta 720 gagataataa atttaatgga acaggaccat gtaaaaatgt cagcacagta caatgtactc 780 atggaattag gccagtaata tcaactcaac tactgttaaa tggcagtcta gcagaagaag 840 aggtagtagt tagatctaaa aatttcacaa acaatgctga agtcataata gtgcagctga 900 aagaatctgt acaaataaat cgtacaagac ccaacaacaa tacaaggaaa agtataccta 960 tgggtccagg gagagcatgg tatgctacag aagatatcat aggaaatata agacaggcac 1020 attgtaacat tagtggagta aaatggaata acactttaca gcaaatagtt aaaaaattaa 1080 gagagcaatt taaaaataaa acaataaagt ttcagccatc ctcaggaggg gacccagaaa 1140 ttgtaaggca cagttttaat tgtagagggg agtttttcta ctgtgataca acactactgt 1200 ttaatagtac ttggaatagt aatgatactt ggaatagtac tgaagggtca aatgacacta 1260 ttacactccc gtgtagaata aaacaaattg taaacatgtg gcaagaagta ggaaaagcaa 1320 tgtatgctcc tcccatcaaa ggacaactta actgttcatc aaatattaca gggccgatat 1380 taacaagaga tggtggtaag ggtgagaact cgaccgagaa caatactgag atattcagac 1440 ctggaggagg agatatgagg gacaattggc gaagtgaatt atataaatat aaagtagtac 1500 aaattgaacc attaggaata gcacccacta aggcaaagag aagagtggtg cagagagaaa 1560 aaagaggagc gggactgttt ttcctggggt tcttgggaac agcaggaagc act 1613 <210> 6 <211> 487 <212> PRT <213> Human immunodeficiency virus type 1 <400> 6 Ser Ala Ile Glu Asn Ser Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Glu Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Ile Lys Leu Glu Asn Val Ser Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Asp Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Tyr Phe Gly Asn Thr Thr Asn             100 105 110 Thr Asn Thr Asn Thr Thr Ser Ser Pro Ser Thr Asn Ser Ser Asn Glu         115 120 125 Gly Glu Val Lys Lys Cys Ser Phe Asn Ile Thr Thr Glu Val Arg Asp     130 135 140 Lys Val Arg Lys Glu Phe Ala Leu Phe Tyr Lys Leu Asp Ile Val Arg 145 150 155 160 Thr Gly His Asp Asn Thr Ser Tyr Arg Leu Ile Ser Cys Asn Thr Ser                 165 170 175 Val Ile Thr Gln Ala Cys Pro Lys Ile Ser Phe Asp Pro Ile Pro Ile             180 185 190 His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Arg Asp Asn         195 200 205 Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys     210 215 220 Thr His Gly Ile Arg Pro Val Ile Ser Thr Gln Leu Leu Leu Asn Gly 225 230 235 240 Ser Leu Ala Glu Glu Glu Val Val Val Arg Ser Lys Asn Phe Thr Asn                 245 250 255 Asn Ala Glu Val Ile Ile Val Gln Leu Lys Glu Ser Val Gln Ile Asn             260 265 270 Arg Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Pro Met Gly Pro         275 280 285 Gly Arg Ala Trp Tyr Ala Thr Glu Asp Ile Ile Gly Asn Ile Arg Gln     290 295 300 Ala His Cys Asn Ile Ser Gly Val Lys Trp Asn Asn Thr Leu Gln Gln 305 310 315 320 Ile Val Lys Lys Leu Arg Glu Gln Phe Lys Asn Lys Thr Ile Lys Phe                 325 330 335 Gln Pro Ser Ser Gly Gly Asp Pro Glu Ile Val Arg His Ser Phe Asn             340 345 350 Cys Arg Gly Glu Phe Phe Tyr Cys Asp Thr Thr Leu Leu Phe Asn Ser         355 360 365 Thr Trp Asn Ser Asn Asp Thr Trp Asn Ser Thr Glu Gly Ser Asn Asp     370 375 380 Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Val Asn Met Trp Gln 385 390 395 400 Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Lys Gly Gln Leu Asn                 405 410 415 Cys Ser Ser Asn Ile Thr Gly Pro Ile Leu Thr Arg Asp Gly Gly Lys             420 425 430 Gly Glu Asn Ser Thr Glu Asn Asn Thr Glu Ile Phe Arg Pro Gly Gly         435 440 445 Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val     450 455 460 Val Gln Ile Glu Pro Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg 465 470 475 480 Val Val Gln Arg Glu Lys Arg                 485 <210> 7 <211> 1595 <212> DNA <213> Human immunodeficiency virus type 1 <400> 7 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tatcagcact 60 tgtggagatg gggcatcatg ctccttggga tgttgatgat ctgtaatgct gcagaacagt 120 tgtgggtcac agtctattat ggggtacctg tgtggaggga tgcaaatacc actctatttt 180 gtgcatccga tgctaaagca tatgatacag aggtacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaag tagtattgga aaatgtgaca gaaagcttta 300 acatatggaa aaataacatg gtagaacaaa tgcatgagga tataatcagt ttgtgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cactctgcgt tactttaaat tgcagtaatt 420 taagtaccac taataataat accattagtg gtaatgagac agcagtaaat aaaggagaaa 480 taaaaaaccg ctctttcaat gtcaccacaa acataagaga tagggtaaag aaagaatatg 540 cgctttttta taatcttgat ttagtacaaa taggtgattc taatactagc tatacaatgg 600 taaagtgtaa cacctcagtc attacacagg cctgtccaaa ggtacccttt gagccaattc 660 ccatacattt ttgtgcccca gctggttttg cgattctaaa gtgtaataat aagacgttca 720 gtggaaaagg agaatgtaca aatgtcagca cagtacaatg tacgcatgga attagaccag 780 tagtatcaac tcatctgctg ttaaatggca gcttagcaga agaagacata gtaattagat 840 ctgacaattt cacggacaat actaaaacca taatagtaca gctagacaat actataaaca 900 ttacttgtac cagacccaac aataatacaa ggaaaggtat acatatagga ccagggagag 960 cattttatgc aacaggggat ataataggaa atataagaca agcacattgt aaccttagta 1020 aaacacattg gaataacact ttaaaacaga tagttaaaaa attaagagaa caatttaaaa 1080 ataaaacaat agtctttaat caatctacag gaggggaccc agaaattgta cagcacactt 1140 ttaattgtag aggggaattt ttctattgta actcaacacc actgtttaat agtacttggt 1200 atcctaatag tacattggat gaaacaaaca gcacagacaa caatgaaact atcacactcc 1260 aatgcagaat aagacaaatt ataaacatgt ggcaggaagt aggaaaagca atgtatgccc 1320 ctcctatcag aggacaaatt acatgcacat caaatattac agggctgata ttaacaagag 1380 atggtggaga taacaatgaa actgagatct tcaggcctgg aggaggcaat atgaaggata 1440 attggagaag tgaattatat aaatataaag tagtaaaaat tgagccatta ggaatagcac 1500 ccactaaggc aaagagaaga gcggtgcaga gagaaaaaag agcagcggga ataggagctg 1560 tgttccttgg gttcttggga gcagcaggaa gcact 1595 <210> 8 <211> 479 <212> PRT <213> Human immunodeficiency virus type 1 <400> 8 Asn Ala Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Arg Asp Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Glu Asn Val Thr Glu Ser     50 55 60 Phe Asn Ile Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Ser Asn Leu Ser Thr Thr Asn Asn Asn             100 105 110 Thr Ile Ser Gly Asn Glu Thr Ala Val Asn Lys Gly Glu Ile Lys Asn         115 120 125 Arg Ser Phe Asn Val Thr Thr Asn Ile Arg Asp Arg Val Lys Lys Glu     130 135 140 Tyr Ala Leu Phe Tyr Asn Leu Asp Leu Val Gln Ile Gly Asp Ser Asn 145 150 155 160 Thr Ser Tyr Thr Met Val Lys Cys Asn Thr Ser Val Ile Thr Gln Ala                 165 170 175 Cys Pro Lys Val Pro Phe Glu Pro Ile Pro Ile His Phe Cys Ala Pro             180 185 190 Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Ser Gly Lys         195 200 205 Gly Glu Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg     210 215 220 Pro Val Val Ser Thr His Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu 225 230 235 240 Asp Ile Val Ile Arg Ser Asp Asn Phe Thr Asp Asn Thr Lys Thr Ile                 245 250 255 Ile Val Gln Leu Asp Asn Thr Ile Asn Ile Thr Cys Thr Arg Pro Asn             260 265 270 Asn Asn Thr Arg Lys Gly Ile His Ile Gly Pro Gly Arg Ala Phe Tyr         275 280 285 Ala Thr Gly Asp Ile Ile Gly Asn Ile Arg Gln Ala His Cys Asn Leu     290 295 300 Ser Lys Thr His Trp Asn Asn Thr Leu Lys Gln Ile Val Lys Lys Leu 305 310 315 320 Arg Glu Gln Phe Lys Asn Lys Thr Ile Val Phe Asn Gln Ser Thr Gly                 325 330 335 Gly Asp Pro Glu Ile Val Gln His Thr Phe Asn Cys Arg Gly Glu Phe             340 345 350 Phe Tyr Cys Asn Ser Thr Pro Leu Phe Asn Ser Thr Trp Tyr Pro Asn         355 360 365 Ser Thr Leu Asp Glu Thr Asn Ser Thr Asp Asn Asn Glu Thr Ile Thr     370 375 380 Leu Gln Cys Arg Ile Arg Gln Ile Ile Asn Met Trp Gln Glu Val Gly 385 390 395 400 Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Gln Ile Thr Cys Thr Ser                 405 410 415 Asn Ile Thr Gly Leu Ile Leu Thr Arg Asp Gly Gly Asp Asn Asn Glu             420 425 430 Thr Glu Ile Phe Arg Pro Gly Gly Gly Asn Met Lys Asp Asn Trp Arg         435 440 445 Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Ile     450 455 460 Ala Pro Thr Lys Ala Lys Arg Arg Ala Val Gln Arg Glu Lys Arg 465 470 475 <210> 9 <211> 1676 <212> DNA <213> Human immunodeficiency virus type 1 <400> 9 agaaagagca gaagacagtg gcaatgaaag tgaaggagac caggaagaat tatcaaagct 60 tgtggagagg gggcaccttg ttccttggaa tgttgatgat ctgtagtgtt acaggacaat 120 tgtgggttac agtctattat ggggtacctg tgtggaaaga ggcaaccacc actctatttt 180 gtgcatcaaa tgctaaagca tatgatacag aggtacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac gcacaagaag tagtattaga aaatgtgaca gaatattttg 300 acatgtggaa aaatgacatg gtagaacaaa tgcatgagga tgtaatcagt ttatgggatc 360 aaagcctaaa gccatgtgta gaattaaccc cactctgtgt tactttaaat tgcactgatg 420 tgaatattac taataccaat aatagtacca ttaacaatag tagtaataat accaatagta 480 gtgattggga acggatggag ccaggagaaa taaaaaactg ctctttcaat agcaccacaa 540 acatgagaga taggacgcag agagaatacg cactttttta taaacttgat atagaaccag 600 tagataataa aagtaataat aaaagtctta atgaaagtat tagtaaaagt attacttata 660 ggttaataag ttataacacc tcagtcatta aacaggcctg tccaaaagta tcttttgagc 720 caattcccat acattattgt gccccagctg gttttgcaat tctaaagtgt aataatgaga 780 cattcgatgg aaaaggagaa tgtagaaatg tcagcacagt acaatgtaca catggaatta 840 ggccaatagt gtcaactcaa ctgctgttaa atggcagtct agcagaaaag gacatagtaa 900 ttagatcaaa caatttctcg gacaatgcta aaaccataat agtacatctg aatgaatcta 960 taacaattaa gtgtataaga cccaacaata atacaagaaa aagtatacat atagcaccag 1020 gaagcgcatt ttatgcaaca ggagacataa taggagatat aaggcaagca cattgtaaca 1080 ttagtgcaaa aaattggatt aacactttaa aacagatagt tataaaacta aaaggaaaat 1140 ataatactag tacaaaaata gactttaagc catcctcagg aggggaccca gaaattgtaa 1200 tgcacagctt taattgtgga ggggagtttt tctactgtaa tacatcaaaa ctgtttaata 1260 atacttggaa ggagaataat actttagagt caaatgatac tatggagatc attaacgaaa 1320 ctattatact cccatgtaga ataaaacagt ttataaacat gtggcagaaa gtgggaaaag 1380 caatgtatgc ccctcccatc agaggacaaa ttaaatgtga atcaaatatt acagggctgc 1440 tattaacaag agatggtggt aatacaaata gcacgaacgg gaccgagacc ttcagacctg 1500 gaggaggaaa tatgaaagac aattggagaa gtgaattgta caaatataaa gtagtaaaaa 1560 ttgaaccaat aggaatagca cccaccaggg caaaaagaag agtggtgcag agagaaaaaa 1620 gagcagtggg aataggagct gtgttccttg ggttcttggg agcagcagga agcact 1676 <210> 10 <211> 506 <212> PRT <213> Human immunodeficiency virus type 1 <400> 10 Ser Val Thr Gly Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asn Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Ala Gln Glu Val Val Leu Glu Asn Val Thr Glu Tyr     50 55 60 Phe Asp Met Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Val 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Glu Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Val Asn Ile Thr Asn Thr Asn             100 105 110 Asn Ser Thr Ile Asn Asn Ser Ser Asn Asn Thr Asn Ser Ser Asp Trp         115 120 125 Glu Arg Met Glu Pro Gly Glu Ile Lys Asn Cys Ser Phe Asn Ser Thr     130 135 140 Thr Asn Met Arg Asp Arg Thr Gln Arg Glu Tyr Ala Leu Phe Tyr Lys 145 150 155 160 Leu Asp Ile Glu Pro Val Asp Asn Lys Ser Asn Asn Lys Ser Leu Asn                 165 170 175 Glu Ser Ile Ser Lys Ser Ile Thr Tyr Arg Leu Ile Ser Tyr Asn Thr             180 185 190 Ser Val Ile Lys Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro         195 200 205 Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn     210 215 220 Glu Thr Phe Asp Gly Lys Gly Glu Cys Arg Asn Val Ser Thr Val Gln 225 230 235 240 Cys Thr His Gly Ile Arg Pro Ile Val Ser Thr Gln Leu Leu Leu Asn                 245 250 255 Gly Ser Leu Ala Glu Lys Asp Ile Val Ile Arg Ser Asn Asn Phe Ser             260 265 270 Asp Asn Ala Lys Thr Ile Ile Val His Leu Asn Glu Ser Ile Thr Ile         275 280 285 Lys Cys Ile Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile His Ile Ala     290 295 300 Pro Gly Ser Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg 305 310 315 320 Gln Ala His Cys Asn Ile Ser Ala Lys Asn Trp Ile Asn Thr Leu Lys                 325 330 335 Gln Ile Val Ile Lys Leu Lys Gly Lys Tyr Asn Thr Ser Thr Lys Ile             340 345 350 Asp Phe Lys Pro Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ser         355 360 365 Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Lys Leu Phe     370 375 380 Asn Asn Thr Trp Lys Glu Asn Asn Thr Leu Glu Ser Asn Asp Thr Met 385 390 395 400 Glu Ile Ile Asn Glu Thr Ile Ile Leu Pro Cys Arg Ile Lys Gln Phe                 405 410 415 Ile Asn Met Trp Gln Lys Val Gly Lys Ala Met Tyr Ala Pro Pro Ile             420 425 430 Arg Gly Gln Ile Lys Cys Glu Ser Asn Ile Thr Gly Leu Leu Leu Thr         435 440 445 Arg Asp Gly Gly Asn Thr Asn Ser Thr Asn Gly Thr Glu Thr Phe Arg     450 455 460 Pro Gly Gly Gly Asn Met Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys 465 470 475 480 Tyr Lys Val Val Lys Ile Glu Pro Ile Gly Ile Ala Pro Thr Arg Ala                 485 490 495 Lys Arg Arg Val Val Gln Arg Glu Lys Arg             500 505 <210> 11 <211> 1646 <212> DNA <213> Human immunodeficiency virus type 1 <400> 11 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagagt tgcttgtgga 60 aatggggcac cttgttcctt ggaatgttga tgatctgtag tgctgtagaa caattgtggg 120 tcacagttta ttatggagta cctgtgtgga aagaagcaac caccactcta ttttgtgcat 180 cagatgctaa ggcatatatt ccagaggtac ataatgtatg ggccacacat gcctgtgtac 240 ccacagatcc caacccacaa gaagtagaat tgaaaaatgt gacagaggat tttaacatgt 300 ggaagaataa catggtagaa caaatgcatg aagatgtaat cagtttatgg gatcaaagcc 360 taaagccata tgtggaatta accccactct gtgttacgtt aaattgcact gattattggg 420 gggatactac tcgtgccgga aatactactg ctagtgtcac tagtactgct aatgtcacta 480 gtagtaaaga ggtacaaatg aaaaactgct ctttctatgt ctccacaaac atgatggata 540 agaaacagaa agaatacgca cttttttata aacttgatgt agtgccaata ggtaatgaga 600 ctaatggtaa ggagactaat aatagctata ggttaataag ttgtaacacc tcagtagtta 660 cccaagcctg tccaaaggta acctttgagc caattcccat acattattgt gccccggctg 720 gttttgtgat tctaaagtgc aaggataaga ggttcaatgg aacaggacca tgtacaaatg 780 tcagcacagt acaatgtaca catggaatta ggccagtagt atcaactcaa ctactgttaa 840 atggcagctt agcagaagaa gatatagtac ttagatctga aaatttctcg aacaatgcta 900 aaaacataat agtacagctg aatgaatctg tagtaattaa ttgtacaaga ctcaacaaca 960 atacaagaaa aagcatacat atggggccag ggaaagcatt ttatgcaaca ggagacacca 1020 taggagatat aagacaagca cattgtaaca ttagtgaaga ggcctggaat aaaactctaa 1080 gacgaatagc tataaaatta aaagaacaat ttaatataac agacaaagta atctttaaac 1140 cctcctcagg aggggacata gaaattgcaa tgcacagtgt taattgtgga ggggaatttt 1200 tctactgtaa tacaacacag ctgtttaata gtacttggaa tgaaacacag ctgaatagta 1260 gtactgtgaa taatattaca aggtcagaca acaacatcac actcccatgc aaaataaagc 1320 aaattgtaaa catgtggcag aaaataggaa aagcaatgta tgcccctccc atcagtggac 1380 taattagatg taaatcaaat attacaggga taatattagc aagagatggt ggtaataatg 1440 gcacaaatga tacgaggacc ttcagacctg taggaggaaa tatgaaggac aattggagaa 1500 gtgaattata taaatataaa gtagtaagaa ttgaaccatt aggagtagca cccaccaagg 1560 caaagagaag agtggtgcag agagaaaaaa gagcagtggg actaggagct atgttccttg 1620 ggttcttggg agcagcagga agcact 1646 <210> 12 <211> 498 <212> PRT <213> Human immunodeficiency virus type 1 <400> 12 Ser Ala Val Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Ile Pro Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Glu Leu Lys Asn Val Thr Glu Asp     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Val 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Tyr Val Glu Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Tyr Trp Gly Asp Thr Thr Arg             100 105 110 Ala Gly Asn Thr Thr Ala Ser Val Thr Ser Thr Ala Asn Val Thr Ser         115 120 125 Ser Lys Glu Val Gln Met Lys Asn Cys Ser Phe Tyr Val Ser Thr Asn     130 135 140 Met Met Asp Lys Lys Gln Lys Glu Tyr Ala Leu Phe Tyr Lys Leu Asp 145 150 155 160 Val Val Pro Ile Gly Asn Glu Thr Asn Gly Lys Glu Thr Asn Asn Ser                 165 170 175 Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val Val Thr Gln Ala Cys Pro             180 185 190 Lys Val Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly         195 200 205 Phe Val Ile Leu Lys Cys Lys Asp Lys Arg Phe Asn Gly Thr Gly Pro     210 215 220 Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val 225 230 235 240 Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Asp Ile                 245 250 255 Val Leu Arg Ser Glu Asn Phe Ser Asn Asn Ala Lys Asn Ile Val             260 265 270 Gln Leu Asn Glu Ser Val Val Ile Asn Cys Thr Arg Leu Asn Asn Asn         275 280 285 Thr Arg Lys Ser Ile His Met Gly Pro Gly Lys Ala Phe Tyr Ala Thr     290 295 300 Gly Asp Thr Ile Gly Asp Ile Arg Gln Ala His Cys Asn Ile Ser Glu 305 310 315 320 Glu Ala Trp Asn Lys Thr Leu Arg Arg Ile Ala Ile Lys Leu Lys Glu                 325 330 335 Gln Phe Asn Ile Thr Asp Lys Val Ile Phe Lys Pro Ser Ser Gly Gly             340 345 350 Asp Ile Glu Ile Ala Met His Ser Val Asn Cys Gly Gly Glu Phe Phe         355 360 365 Tyr Cys Asn Thr Thr Gln Leu Phe Asn Ser Thr Trp Asn Glu Thr Gln     370 375 380 Leu Asn Ser Ser Thr Val Asn Asn Ile Thr Arg Ser Asp Asn Asn Ile 385 390 395 400 Thr Leu Pro Cys Lys Ile Lys Gln Ile Val Asn Met Trp Gln Lys Ile                 405 410 415 Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly Leu Ile Arg Cys Lys             420 425 430 Ser Asn Ile Thr Gly Ile Ile Leu Ala Arg Asp Gly Gly Asn Asn Gly         435 440 445 Thr Asn Asp Thr Arg Thr Phe Arg Pro Val Gly Gly Asn Met Lys Asp     450 455 460 Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Pro 465 470 475 480 Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu                 485 490 495 Lys arg          <210> 13 <211> 1586 <212> DNA <213> Human immunodeficiency virus type 1 <400> 13 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tgtcagcgct 60 tgtggaaatg gggcaccatg ctccttggga tgttaatgat ctgtagggct gcagagcaat 120 tgtgggtcac agtctattat ggagtacctg tgtggagaga agcaaacacc actctatttt 180 gtgcatcaga tgctaaagca tatgatacag aggtacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccctaac ccacaagaag tagtattgga aaatgtgaca gaaaatttta 300 acatgtggaa aaataacatg gtagaacaga tgcatgagga tataatcagt ctatgggatc 360 aaagcctaaa accatgtgta aaattaaccc cactctgtgt tactttaaat tgtaatacca 420 ttaatgccac taaagatatg ataggagaat taaaaaactg ctctttcaac atcaccacaa 480 gcataagaga taagtggcaa aaagaatatg cactttttta taaacttgat gtagtgccaa 540 tagatgataa tggtaatgat actggtaatg gtagctatag gctaataagt tgtaatacct 600 cagtcattac acaggcctgt ccaaagacat cctttgagcc aattcccata cattattgtg 660 ccccggctgg ttttgcgatt ctaaagtgta acaataaaaa gttcaatgga acaggaccac 720 gtaaaaatgt cagcacagta caatgtacac atggaattag gccagtagta tctactcaac 780 tgttgttaaa tggcagtcta gcagaagaag agatagtact tagatctgaa aatttctcaa 840 acaatgctaa aaccataata gtacaattga atgaatctat agtaattaat tgtacaagac 900 ccaacaacaa tacgagaaaa agtatacata taggaccagg gagagcattt tatgcagcag 960 gagaaataat aggagatata agaacagcac attgtaacat tagtggaaca aaatggaata 1020 acactttaaa acagatagtt gtaaaattaa gagaacaatt tggaaataaa acaatggtct 1080 ttagtcactc ctcaggaggg gacccggaaa ttgtaaggca cagttttaat tgtggagggg 1140 aatttttcca ttgcaataca acacaactgt ttaatagtag ttggccttgg aatggtactg 1200 aagggtcaaa taacactgaa ggaaatgaca caatcaccct cccatgcaga ataaaacaaa 1260 ttataaacat gtggcaggaa gtaggaaaag caatgtatgc ccctcccatc agaggggtaa 1320 ttaaatgttc atcaaatatt acagggctat tattaacaag agatgggggt actaacagga 1380 ccgacaatgg gagcgaggtc ttcagacctg ggggaggaga tatgagggac aattggagta 1440 gtgaattata taaaaataaa gtagtaagaa ttgaaccatt aggagtagca cccaccaagg 1500 caaagagaag agtggtgcag agagaaaaaa gagcagtggg actaggagct atgttccttg 1560 ggttcttggg agcagcagga agcact 1586 <210> 14 <211> 476 <212> PRT <213> Human immunodeficiency virus type 1 <400> 14 Arg Ala Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Arg Glu Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Asn Thr Ile Asn Ala Thr Lys Asp Met             100 105 110 Ile Gly Glu Leu Lys Asn Cys Ser Phe Asn Ile Thr Thr Ser Ile Arg         115 120 125 Asp Lys Trp Gln Lys Glu Tyr Ala Leu Phe Tyr Lys Leu Asp Val Val     130 135 140 Pro Ile Asp Asp Asn Gly Asn Asp Thr Gly Asn Gly Ser Tyr Arg Leu 145 150 155 160 Ile Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Thr Ser                 165 170 175 Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile             180 185 190 Leu Lys Cys Asn Asn Lys Lys Phe Asn Gly Thr Gly Pro Arg Lys Asn         195 200 205 Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr     210 215 220 Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Ile Val Leu Arg 225 230 235 240 Ser Glu Asn Phe Ser Asn Asn Ala Lys Thr Ile Ile Val Gln Leu Asn                 245 250 255 Glu Ser Ile Val Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys             260 265 270 Ser Ile His Ile Gly Pro Gly Arg Ala Phe Tyr Ala Ala Gly Glu Ile         275 280 285 Ile Gly Asp Ile Arg Thr Ala His Cys Asn Ile Ser Gly Thr Lys Trp     290 295 300 Asn Asn Thr Leu Lys Gln Ile Val Val Lys Leu Arg Glu Gln Phe Gly 305 310 315 320 Asn Lys Thr Met Val Phe Ser His Ser Ser Gly Gly Asp Pro Glu Ile                 325 330 335 Val Arg His Ser Phe Asn Cys Gly Gly Glu Phe Phe His Cys Asn Thr             340 345 350 Thr Gln Leu Phe Asn Ser Ser Trp Pro Trp Asn Gly Thr Glu Gly Ser         355 360 365 Asn Asn Thr Glu Gly Asn Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys     370 375 380 Gln Ile Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro 385 390 395 400 Pro Ile Arg Gly Val Ile Lys Cys Ser Ser Asn Ile Thr Gly Leu Leu                 405 410 415 Leu Thr Arg Asp Gly Gly Thr Asn Arg Thr Asp Asn Gly Ser Glu Val             420 425 430 Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Ser Ser Glu Leu         435 440 445 Tyr Lys Asn Lys Val Val Arg Ile Glu Pro Leu Gly Val Ala Pro Thr     450 455 460 Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg 465 470 475 <210> 15 <211> 1618 <212> DNA <213> Human immunodeficiency virus type 1 <400> 15 agaaagagcg aagacagtgg caatgagagt gagggggatc atgaggaatt atcagtactt 60 atggaaatgg ggcaccatgc tcctggggat attgatgatc tgtaatgcta gtgaaaaatt 120 gtgggtcaca gtctattatg gggtacctgt gtggaaagag gcaaacacca ctctattttg 180 tgcatcagat gccaaagctt atgatacaga agtacataat gtttgggcca cacatgcctg 240 tgtacccaca gacccccgcc ctcaagaagt actattggga aatgtgacag aaaattttaa 300 catgtggaaa aataacatgg tagaacaaat gcatgaggat ataatcagtt tatgggatca 360 aagcctaaag ccatgtgtaa aattaacccc actctgtgtt actttaaatt gcactaactt 420 gaatgatact aatatcagta gtagtaatgt tagtacccat aatagtagtg gcataggaga 480 aatgaaaaat tgctctttca atgttaccac aagtataaga gataagatga agaaagaata 540 tgcacttttt tatagacttg atatagttcc aatagataat agtaacacca gttatatgtt 600 aataagttgt aatacctcag tcattacaca ggcctgtcca aaggtatcct ttgaaccaat 660 tcccatacat tattgtgccc cggctggttt tgcgattcta aagtgtaatg ataagaagtt 720 caatggaaca ggaccatgta agaatgtcag cacagtacaa tgtacacatg gaattaggcc 780 agtagtatca actcaactgc tgttaaatgg cagtttagca gaagaagaga tagtaattag 840 atctgaaaat ttcacagaca atactaaaac cataatagtg catctgaacg aatctataca 900 aattaattgt acaagaccca acaacaatac aagaaaaagc atacatatag gaccaggaag 960 agcattttat gcaacaggag aaataatagg agatataaga caagcacatt gtaaccttag 1020 tagagcaaaa tggaataaca cgttaaaaca gatagttaaa aaattaagag tacaatttga 1080 aaataaaaca atagtcttta atcaatcttc aggaggggac ccagaaattg taatgcacag 1140 ctttaattgt ggaggggaat ttttctactg taatacaaca gcactgttta atagtacttg 1200 gaatagtaat agtactgaat ggtcaaatga cactgaaagc aatgacacag tgattacact 1260 cccatgcaga ataaaacaaa tagtaaacat gtggcaggaa gttggaaaag caatgtatgc 1320 ccctcccatc aagggacaaa ttaagtggat atcaaatatt acagggatac tattaacaag 1380 agatggggga agagatgagg ttaatagcac gaacgagaac aagaccgaga tcttcagacc 1440 tgcaggagga aatatgaagg acaattggag aagtgaatta tataaatata aagtagtaaa 1500 aattgaacca ttaggaatag cacccactag ggcaagaaga agagtggtgc agagagaaaa 1560 aagagcagtg acactaggag ctttgttcct tgggttcttg ggagcagcag gaagcact 1618 <210> 16 <211> 487 <212> PRT <213> Human immunodeficiency virus type 1 <400> 16 Asn Ala Ser Glu Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Arg Pro Gln Glu Val Leu Leu Gly Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asn Leu Asn Asp Thr Asn Ile Ser             100 105 110 Ser Ser Asn Val Ser Thr His Asn Ser Ser Gly Ile Gly Glu Met Lys         115 120 125 Asn Cys Ser Phe Asn Val Thr Thr Ser Ile Arg Asp Lys Met Lys Lys     130 135 140 Glu Tyr Ala Leu Phe Tyr Arg Leu Asp Ile Val Pro Ile Asp Asn Ser 145 150 155 160 Asn Thr Ser Tyr Met Leu Ile Ser Cys Asn Thr Ser Val Ile Thr Gln                 165 170 175 Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala             180 185 190 Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Lys Phe Asn Gly         195 200 205 Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile     210 215 220 Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu 225 230 235 240 Glu Glu Ile Val Ile Arg Ser Glu Asn Phe Thr Asp Asn Thr Lys Thr                 245 250 255 Ile Ile Val His Leu Asn Glu Ser Ile Gln Ile Asn Cys Thr Arg Pro             260 265 270 Asn Asn Asn Thr Arg Lys Ser Ile His Ile Gly Pro Gly Arg Ala Phe         275 280 285 Tyr Ala Thr Gly Glu Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn     290 295 300 Leu Ser Arg Ala Lys Trp Asn Asn Thr Leu Lys Gln Ile Val Lys Lys 305 310 315 320 Leu Arg Val Gln Phe Glu Asn Lys Thr Ile Val Phe Asn Gln Ser Ser                 325 330 335 Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys Gly Gly Glu             340 345 350 Phe Phe Tyr Cys Asn Thr Thr Ala Leu Phe Asn Ser Thr Trp Asn Ser         355 360 365 Asn Ser Thr Glu Trp Ser Asn Asp Thr Glu Ser Asn Asp Thr Val Ile     370 375 380 Thr Leu Pro Cys Arg Ile Lys Gln Ile Val Asn Met Trp Gln Glu Val 385 390 395 400 Gly Lys Ala Met Tyr Ala Pro Pro Ile Lys Gly Gln Ile Lys Trp Ile                 405 410 415 Ser Asn Ile Thr Gly Ile Leu Leu Thr Arg Asp Gly Gly Arg Asp Glu             420 425 430 Val Asn Ser Thr Asn Glu Asn Lys Thr Glu Ile Phe Arg Pro Ala Gly         435 440 445 Gly Asn Met Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val     450 455 460 Val Lys Ile Glu Pro Leu Gly Ile Ala Pro Thr Arg Ala Arg Arg Arg 465 470 475 480 Val Val Gln Arg Glu Lys Arg                 485 <210> 17 <211> 1625 <212> DNA <213> Human immunodeficiency virus type 1 <400> 17 agaaagagca gaagacagtg gcaatgagag tgaaggagat caagaagaat tgtcagcgct 60 tgtggagatg gggcatcatg ctccttggga tattgatgat ctgtagtgct acagaaaaat 120 tgtgggtcac agtctattat ggggtacctg tgtggaagga agcaaacacc actctatttt 180 gtgcatctga tgctaaagca tatgatacag aggtacataa tgtttgggca acacatgcct 240 gtgtacccac agaccccaac ccacaagaag taagattaaa aaatgtgaca gaaaatttta 300 acatgtggag gaataacatg gtagaacaga tgcaggagga tataatcagt ttgtgggatc 360 aaagcctaaa gccatgtgta acattaactc cactatgtgt tactttaaat tgcactgatt 420 attggggcaa tgttactggg accaatacta ctagtaaccc tactggtact ggtgtgggtg 480 gtaccactaa caatggcgcg gaagtgatga agtgctcttt taatgtcacc acaagtgtaa 540 gagataaggt acaaaaagaa tctgctcttt tttatagact tgatgtagta aaaatagatg 600 agaaaacaaa tacaaccaat tataggttga taagttgtaa cacctcagtc attaaacagg 660 cccgtccaaa ggtaaacttt gagccaattc ccatacatta ttgtgccccg gctggttttg 720 cgattctaaa gtgtaatgat aagaagttca atggaacagg atcatgtaaa aatgtcagca 780 cagtacaatg tacacatgga attaagccag tagtatccac tcacttgctg ttaaatggca 840 gtctagcaga agatgagata gtaattagat ctgaaaattt cacgaacaat gctaaaacca 900 taatagtaca gctgaataat tatgtaaaaa ttaattgtat aagacccaat aataatacaa 960 gaaaaagtat atcactcgga ccaggaagag cattttatac aacaggagac ataataggaa 1020 atataagaca agcacattgc aaccttagtg gtacagaatg gaataacact ttaaaacagg 1080 tagctaacaa attaagagaa caatttaaca aaacaataat aaaatttaag caaccccccc 1140 cgggagggga cctagaaatc acaatgctca cttttaattg tggaggagaa tttttttact 1200 gtaattcatc agcactgttt aatagtactt tgacttggga tagtaaggca tgggcaaata 1260 cacttgaaga aaatatcaca ctcccatgca gaataaaaca aattgtaaac aagtggcagg 1320 aagtaggaaa agcaatatat gcccctccca tcagtggaca gattaattgt acatcaaata 1380 ttacagggat actattaaca agagatggtg gtaataacaa cgacactaac aacactgagg 1440 tcttcagacc tggaggagga gatatgaggg acaattggag aagtgagtta tataaatata 1500 aagtagtaaa aattgaacca ttaggaatag cacccaccag ggcaaagaga agagtggtgc 1560 agagagaaaa aagagcagca ataggagcta tgttccttgg gttcttggga gcagcaggaa 1620 gcact 1625 <210> 18 <211> 490 <212> PRT <213> Human immunodeficiency virus type 1 <400> 18 Ser Ala Thr Glu Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Arg Leu Lys Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Arg Asn Asn Met Val Glu Gln Met Gln Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Thr Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Tyr Trp Gly Asn Val Thr Gly             100 105 110 Thr Asn Thr Thr Ser Asn Pro Thr Gly Thr Gly Val Gly Gly Thr Thr         115 120 125 Asn Asn Gly Ala Glu Val Met Lys Cys Ser Phe Asn Val Thr Thr Ser     130 135 140 Val Arg Asp Lys Val Gln Lys Glu Ser Ala Leu Phe Tyr Arg Leu Asp 145 150 155 160 Val Val Lys Ile Asp Glu Lys Thr Asn Thr Thr Asn Tyr Arg Leu Ile                 165 170 175 Ser Cys Asn Thr Ser Val Ile Lys Gln Ala Arg Pro Lys Val Asn Phe             180 185 190 Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu         195 200 205 Lys Cys Asn Asp Lys Lys Phe Asn Gly Thr Gly Ser Cys Lys Asn Val     210 215 220 Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr His 225 230 235 240 Leu Leu Leu Asn Gly Ser Leu Ala Glu Asp Glu Ile Val Ile Arg Ser                 245 250 255 Glu Asn Phe Thr Asn Asn Ala Lys Thr Ile Ile Val Gln Leu Asn Asn             260 265 270 Tyr Val Lys Ile Asn Cys Ile Arg Pro Asn Asn Asn Thr Arg Lys Ser         275 280 285 Ile Ser Leu Gly Pro Gly Arg Ala Phe Tyr Thr Thr Gly Asp Ile Ile     290 295 300 Gly Asn Ile Arg Gln Ala His Cys Asn Leu Ser Gly Thr Glu Trp Asn 305 310 315 320 Asn Thr Leu Lys Gln Val Ala Asn Lys Leu Arg Glu Gln Phe Asn Lys                 325 330 335 Thr Ile Ile Lys Phe Lys Gln Pro Pro Pro Gly Gly Asp Leu Glu Ile             340 345 350 Thr Met Leu Thr Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser         355 360 365 Ser Ala Leu Phe Asn Ser Thr Leu Thr Trp Asp Ser Lys Ala Trp Ala     370 375 380 Asn Thr Leu Glu Glu Asn Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile 385 390 395 400 Val Asn Lys Trp Gln Glu Val Gly Lys Ala Ile Tyr Ala Pro Pro Ile                 405 410 415 Ser Gly Gln Ile Asn Cys Thr Ser Asn Ile Thr Gly Ile Leu Leu Thr             420 425 430 Arg Asp Gly Gly Asn Asn Asn Asp Thr Asn Asn Thr Glu Val Phe Arg         435 440 445 Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys     450 455 460 Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Ile Ala Pro Thr Arg Ala 465 470 475 480 Lys Arg Arg Val Val Gln Arg Glu Lys Arg                 485 490 <210> 19 <211> 1643 <212> DNA <213> Human immunodeficiency virus type 1 <400> 19 agaaagagca gaagacagtg gcaatgagag tgatggagat caggaagagt tatcagaact 60 tatggagagg gggcaccttg ctccttggga tgttaatgat gatctgtagt gctgcagaag 120 aatcgtgggt cacagtatat tatggggtac ctgtgtggaa agaagcaacc accactctat 180 tttgtgcatc agatgctaaa ggctatgata cagaaagaca taatgtttgg gccacacatg 240 cctgtgtacc cacagacccc aacccacaag aaattgaatt ggtaaatgtg acagaatatt 300 ttaacatggg aaaaaataac atggtagaac agatgcatga ggatataatc agtttatggg 360 atgaaagcct aaagccatgt gtaaaattaa ccccactctg tgttactcta aattgcacta 420 atttgaatat tactaatacc actggtatta ctaatagtag cctggaagaa atgaggagaa 480 taatgacaaa ctgttctttc aaggtcacca caaatataag agataaggtg cagaagcaat 540 atgcactgtt gtataaactt gatgtagtac aaatagatga tgagagtacc acaggtaata 600 ggagtaacag cgcctacagg ttgataagtt gtaacacctc agtcattaca caggcccgtc 660 caaaggtatc ctttgagcca attcccatac acttttgtgc cccggctggt tttgcgattc 720 taaaatgtaa ggataagaag ttcaatggaa caggactatg taaaaatgtc agcacagtac 780 aatgtacaca tggaattagg ccagtagtat caactcagct gctgttaaat ggcagtctag 840 cagaagaaga ggtagtaatt agatctgtaa atttcacaaa caatgctaaa actataatag 900 tacagctgaa caaatctata gaaattaatt gtacaagacc caacaacaat acaagaagag 960 gtataaatat aggacccggg agagcatttt acacaataaa ggacataaca ggagatataa 1020 gacaagcaca ttgtaacatt agtgcatcag actggaataa tactgtaaca caggtagttg 1080 caaaattaaa agagcaattt gggaataaaa caatagtctt taatcaatcc tcaggaggag 1140 acccagaaat tataatgcac acttttaatt gtggagggga atttttctac tgtaagacaa 1200 cacaactgtt taatagtact tggcctaata atggtacttg gcctaatagt aattggactg 1260 ataataatag aacttggaac ggtgctaaag gaactatcac actcccatgc agaataaaac 1320 aaattgtaaa catgtggcag gaagtaggaa aagcaatgta tgcccctccc atcgaaggga 1380 aaataaaatg tacatcaaat cttacaggat tgctattaac aagagatggt ggtaatgtga 1440 atggcaccac catcgagacc ttcagacctg gaggaggaga tatgagggac aattggagaa 1500 gtgaattata taaatataaa gtagtacaaa ttgaaccatt aggactggca cctaccaagg 1560 caaagagaag agtggtgcag agagaaaaaa ggggagtaat aggagctatg ttccttgggt 1620 tcttgggagc agcaggaagc act 1643 <210> 20 <211> 495 <212> PRT <213> Human immunodeficiency virus type 1 <400> 20 Ser Ala Ala Glu Glu Ser Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Gly             20 25 30 Tyr Asp Thr Glu Arg His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Ile Glu Leu Val Asn Val Thr Glu Tyr     50 55 60 Phe Asn Met Gly Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asn Leu Asn Ile Thr Asn Thr Thr             100 105 110 Gly Ile Thr Asn Ser Ser Leu Glu Glu Met Arg Arg Ile Met Thr Asn         115 120 125 Cys Ser Phe Lys Val Thr Thr Asn Ile Arg Asp Lys Val Gln Lys Gln     130 135 140 Tyr Ala Leu Leu Tyr Lys Leu Asp Val Val Gln Ile Asp Asp Glu Ser 145 150 155 160 Thr Thr Gly Asn Arg Ser Asn Ser Ala Tyr Arg Leu Ile Ser Cys Asn                 165 170 175 Thr Ser Val Ile Thr Gln Ala Arg Pro Lys Val Ser Phe Glu Pro Ile             180 185 190 Pro Ile His Phe Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Lys         195 200 205 Asp Lys Lys Phe Asn Gly Thr Gly Leu Cys Lys Asn Val Ser Thr Val     210 215 220 Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu 225 230 235 240 Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser Val Asn Phe                 245 250 255 Thr Asn Asn Ala Lys Thr Ile Ile Val Gln Leu Asn Lys Ser Ile Glu             260 265 270 Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Arg Gly Ile Asn Ile         275 280 285 Gly Pro Gly Arg Ala Phe Tyr Thr Ile Lys Asp Ile Thr Gly Asp Ile     290 295 300 Arg Gln Ala His Cys Asn Ile Ser Ala Ser Asp Trp Asn Asn Thr Val 305 310 315 320 Thr Gln Val Val Ala Lys Leu Lys Glu Gln Phe Gly Asn Lys Thr Ile                 325 330 335 Val Phe Asn Gln Ser Ser Gly Gly Asp Pro Glu Ile Ile Met His Thr             340 345 350 Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Lys Thr Thr Gln Leu Phe         355 360 365 Asn Ser Thr Trp Pro Asn Asn Gly Thr Trp Pro Asn Ser Asn Trp Thr     370 375 380 Asp Asn Asn Arg Thr Trp Asn Gly Ala Lys Gly Thr Ile Thr Leu Pro 385 390 395 400 Cys Arg Ile Lys Gln Ile Val Asn Met Trp Gln Glu Val Gly Lys Ala                 405 410 415 Met Tyr Ala Pro Pro Ile Glu Gly Lys Ile Lys Cys Thr Ser Asn Leu             420 425 430 Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Val Asn Gly Thr Thr         435 440 445 Ile Glu Thr Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg     450 455 460 Ser Glu Leu Tyr Lys Tyr Lys Val Val Gln Ile Glu Pro Leu Gly Leu 465 470 475 480 Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg                 485 490 495 <210> 21 <211> 1626 <212> DNA <213> Human immunodeficiency virus type 1 <400> 21 agaaagagca gaagacagtg gcaatgagag tgatggagat caggaggaat tatcagcgct 60 cgtggagatg gggcaccatg ctccttggga tgttgatgat ttatagtgct gcaggagagt 120 tatgggtcac agtttattat ggggtaccgg tgtggaaaga agcaaccact actttattct 180 gtgcatcaga tgctaaagca tatgacacag aggtacataa tgtttgggca acacatgcct 240 gtgtacccac agaccctaat ccacaagaag tattattgga aaatgtgaca gaaaatttta 300 acatgtggaa aaataacatg gtagaacaga tgcatgagga tataatcagt ctatgggatc 360 aaagcctaaa gccacgtgta aaattaaccc cactctgtgt tactttaaac tgtactaatt 420 tgagaaatgt tactaatttg aaaaatgtta ctaataacag taatattagt ggtactaata 480 acaatactag tagtgggggg ctgaagggag gagaaatgaa aaattgctct ttctatatca 540 ccacacacag aaaggataag gtgaagaaag aatatgcact tttttataac cttgatatag 600 tatcaacaga tgatgataat acaagctata tattgagaag ttgtaacacc tcagtcatta 660 cccaggcctg tccaaaggta acctttgaac caattcccat acattattgt accccagctg 720 gttttgcgat tctgaagtgt aacgataaga agttcaatgg aacaggacca tgtagaaatg 780 tcagtacagt acaatgtaca catggaatca agccagtagt gtcaacccaa ctgttgttaa 840 atggcagtct agcagaagaa gaggtagtaa ttagatctga aaatttcacg gacaatgtta 900 aaaccataat agtacagctg aatgaatctg taataattaa ttgtacaaga cccagcaaca 960 atacaagaaa aagtatacgt tttggaccag gggcggcatt ttatacaaca ggagacataa 1020 taggagatat aagacaagca cattgtaaca tcagtagagc agaatggaat aacactttaa 1080 aacaaatagt taaaaaatta caagaacaat ttgtgaataa aacaatagtc tttaatcaat 1140 ctgcaggagg ggacccagaa attgtaaggc acagtgtaaa ttgtggaggg gaatttttct 1200 actgcgatac aacacaactg tttaatagta cttggaatag tactggagag tcaaataaca 1260 ctcaagaaaa tgacctaatc acactcccat gcagaataaa acaaattata aacagatggc 1320 aggaaatagg aaaagcaatg tatgcccctc ccatccaagg acaaattagc tgtacatcaa 1380 atattacagg gctgctacta acaagagatg gtggtaataa taataacagc acagagacct 1440 tcagacctgg aggaggaaat atgaaggaca attggagaag tgaattatat aaatataaag 1500 tagtaaaaat tcagccatta ggggtagcac ccaccaaggc aaagagaaga gtggtgcaga 1560 gggaaaagag cagtgggagc actaggagct atgttccttg ggttcttggg agcagcagga 1620 agcact 1626 <210> 22 <211> 489 <212> PRT <213> Human immunodeficiency virus type 1 <400> 22 Ser Ala Ala Gly Glu Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Leu Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Arg Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asn Leu Arg Asn Val Thr Asn Leu             100 105 110 Lys Asn Val Thr Asn Asn Ser Asn Ile Ser Gly Thr Asn Asn Asn Thr         115 120 125 Ser Ser Gly Gly Leu Lys Gly Gly Glu Met Lys Asn Cys Ser Phe Tyr     130 135 140 Ile Thr Thr His Arg Lys Asp Lys Val Lys Lys Glu Tyr Ala Leu Phe 145 150 155 160 Tyr Asn Leu Asp Ile Val Ser Thr Asp Asp Asp Asn Thr Ser Tyr Ile                 165 170 175 Leu Arg Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val             180 185 190 Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Thr Pro Ala Gly Phe Ala         195 200 205 Ile Leu Lys Cys Asn Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Arg     210 215 220 Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser 225 230 235 240 Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile                 245 250 255 Arg Ser Glu Asn Phe Thr Asp Asn Val Lys Thr Ile Ile Val Gln Leu             260 265 270 Asn Glu Ser Val Ile Ile Asn Cys Thr Arg Pro Ser Asn Asn Thr Arg         275 280 285 Lys Ser Ile Arg Phe Gly Pro Gly Ala Ala Phe Tyr Thr Thr Gly Asp     290 295 300 Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn Ile Ser Arg Ala Glu 305 310 315 320 Trp Asn Asn Thr Leu Lys Gln Ile Val Lys Lys Leu Gln Glu Gln Phe                 325 330 335 Val Asn Lys Thr Ile Val Phe Asn Gln Ser Ala Gly Gly Asp Pro Glu             340 345 350 Ile Val Arg His Ser Val Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asp         355 360 365 Thr Thr Gln Leu Phe Asn Ser Thr Trp Asn Ser Thr Gly Glu Ser Asn     370 375 380 Asn Thr Gln Glu Asn Asp Leu Ile Thr Leu Pro Cys Arg Ile Lys Gln 385 390 395 400 Ile Ile Asn Arg Trp Gln Glu Ile Gly Lys Ala Met Tyr Ala Pro Pro                 405 410 415 Ile Gln Gly Gln Ile Ser Cys Thr Ser Asn Ile Thr Gly Leu Leu Leu             420 425 430 Thr Arg Asp Gly Gly Asn Asn Asn Asn Ser Thr Glu Thr Phe Arg Pro         435 440 445 Gly Gly Gly Asn Met Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr     450 455 460 Lys Val Val Lys Ile Gln Pro Leu Gly Val Ala Pro Thr Lys Ala Lys 465 470 475 480 Arg Arg Val Val Gln Arg Glu Lys Ser                 485 <210> 23 <211> 1562 <212> DNA <213> Human immunodeficiency virus type 1 <400> 23 agaaagagca gaagacagtg gcaatgagag tgacggggat gaggaacaat tatccgcact 60 tatggaaaga ggtcaccttg ctccttggaa tattgatgat atgtagtgct acagaaaatt 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga agcaaccacc actctattct 180 gtgcatcgga tgctaaggca tatgatacag aggcacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaaa tgagattgga aaatgtgaca gaaaatttta 300 acatgtggaa aaataacatg gtagaacaga tgcaggatga tataatcagt ttatgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cactctgtgt tactttaaat tgcactaata 420 ccacaaatgc taatagtacc aataataata actgggacat gaaaaactgc tctttcaatg 480 tcacctcagg cataagagat aaggtgcgaa aagaacatgc actcttttat gcacttgatg 540 tagtaccaat agataatgag actaactata ggttgataag ttgtaacacc tcagtcatca 600 cacaggcctg tccaaaggta tcctttgagc caattcctat acattattat gccccggctg 660 gttttgcgat tctaaaatgt agggataaaa agttcaatgg aacaggacca tgtaaagatg 720 tcagcacagt acaatgtaca catggaatta agccagtagt atcaactcaa ctactgttaa 780 atggcagtct agcagaagaa gaggtagtaa tcagatctga aaacttcacg aacaatgcta 840 aaaccatatt agtacaactg aatgaatctg tagtaattaa ttgtacaaga cccaacaaca 900 atacaagaaa aagtataaat ataggaccag ggagagcatt ctatgcaaca ggagaaataa 960 taggagatat aagacaagca cattgtaacc ttagtaaggc acaatggaac aacactttaa 1020 aaaaggtagt tgtaaaatta agagaacaat ttccgaataa aacgatagtc tttactcatt 1080 cctcaggagg ggacccagaa attgtaatgc acagttttaa ttgtggagga gaatttttct 1140 actgtaattc aacaccactg tttaatagta cttggaagtt gaatggtact atggaatcaa 1200 atgacactga aggaaatctc acactccaat gcagaataaa acaaatcatg aacaagtggc 1260 aggaagtagg aaaggcaatg tatgcccctc ccatccaagg acagattaga tgttcatcaa 1320 atattacagg gctgttatta gtaagagatg gtggggtcaa cagcgccaac gagaccttca 1380 gaccaggagg aggagatatg agggacaatt ggagaagtga attatataaa tataaagtag 1440 taaaaattga accattagga atagcaccca ccaaggcaaa gagaagagtg gtgcagagag 1500 aaaaaagagc agtgggaata ggagctttgt tccttgggtt cttgggagca gcaggaagca 1560 ct 1562 <210> 24 <211> 468 <212> PRT <213> Human immunodeficiency virus type 1 <400> 24 Ser Ala Thr Glu Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Met Arg Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met Gln Asp Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asn Thr Thr Asn Ala Asn Ser Thr             100 105 110 Asn Asn Asn Asn Trp Asp Met Lys Asn Cys Ser Phe Asn Val Thr Ser         115 120 125 Gly Ile Arg Asp Lys Val Arg Lys Glu His Ala Leu Phe Tyr Ala Leu     130 135 140 Asp Val Val Pro Ile Asp Asn Glu Thr Asn Tyr Arg Leu Ile Ser Cys 145 150 155 160 Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro                 165 170 175 Ile Pro Ile His Tyr Tyr Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys             180 185 190 Arg Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Lys Asp Val Ser Thr         195 200 205 Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu     210 215 220 Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser Glu Asn 225 230 235 240 Phe Thr Asn Asn Ala Lys Thr Ile Leu Val Gln Leu Asn Glu Ser Val                 245 250 255 Val Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Asn             260 265 270 Ile Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly Glu Ile Ile Gly Asp         275 280 285 Ile Arg Gln Ala His Cys Asn Leu Ser Lys Ala Gln Trp Asn Asn Thr     290 295 300 Leu Lys Lys Val Val Val Lys Leu Arg Glu Gln Phe Pro Asn Lys Thr 305 310 315 320 Ile Val Phe Thr His Ser Ser Gly Gly Asp Pro Glu Ile Val Met His                 325 330 335 Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr Pro Leu             340 345 350 Phe Asn Ser Thr Trp Lys Leu Asn Gly Thr Met Glu Ser Asn Asp Thr         355 360 365 Glu Gly Asn Leu Thr Leu Gln Cys Arg Ile Lys Gln Ile Met Asn Lys     370 375 380 Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Gln Gly Gln 385 390 395 400 Ile Arg Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Val Arg Asp Gly                 405 410 415 Gly Val Asn Ser Ala Asn Glu Thr Phe Arg Pro Gly Gly Gly Asp Met             420 425 430 Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile         435 440 445 Glu Pro Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln     450 455 460 Arg Glu Lys Arg 465 <210> 25 <211> 1643 <212> DNA <213> Human immunodeficiency virus type 1 <400> 25 agaaagagca gaagacagtg gcaatgagag cgaaggggat caggaggaat tggcagcgct 60 tgtgttggag atggggcacg atgctccttg gaatgttaat gatctgtagt gctacagaac 120 cattgtgggt aacagtctat tatggggtac ctgtgtggaa agaagcaacc accactctat 180 ttcgtgcatc agatgctaaa gcatatggta cagaggtaca taatgtttgg gccacgcatg 240 cctgtgtacc cacagacccc aacccacaag aagtagtatt ggaaaatgta acagaaaatt 300 ttaatgcgtg ggaaaataac atggtggaac aaatgcatga ggatataatc agtttatggg 360 atcaaagtct aaagccatgt gtaaagttaa ccccactctg tgttacttta aaatgcactg 420 ataatttggg gaatgatact aaaaccagta ataagagctg ggaaaagatg gagccaggag 480 aaataaaaaa ctgctccttc aacatcacca caagcatagg agataagacg caggaaacat 540 atgcattttt ttataaactt gatgtagtac caatagataa taagactaca atagataata 600 atactgcaag aaactatagc gactataggt tgataagttg taacacctca gtcattacac 660 aggcctgtcc aaaggtatct tttgaaccaa ttcccataca ttattgtgcc ccggctggtt 720 ttgcgattct aaagtgtaac aataagacat tcatgggaaa aggaccatgt acaaatgtca 780 gcacagtaca atgtacacat ggaattaagc cagtagtatc aactcaactg ctgttaaatg 840 gcagtctggc agaagaagag ataataatta gatctgaaaa tttcacggac aatgctaaaa 900 ccttaataat acatctgaac cactctgtag aaattaagtg tataagaccc aacaacaata 960 caagcgaagg tatacatata ggaccaggga gagcgtttta tccaacaaga ataataggag 1020 atataagaaa agcacattgt aacattaatg aaacagcatg gaagacaact ttagcacaga 1080 tagttacaaa attaagagaa caatttggga ataaaacaat agtctttagc caatcctcag 1140 gaggggaccc agaaattgta atgcacagtt ttaattgtgg aggggaattt ttctactgtg 1200 atacaacaaa actgtttaat agtacttgga atgttaatga tacttggaat ggtgctggag 1260 ggtcaaacag cactgaaaga aacaccacca tcatactccc atgcaaaata aaacaaatta 1320 taaacttgtg gcaggaggta ggaaaagcaa tgtatgcccc tcccatcaaa ggactaatta 1380 gatgttcatc aaatattaca gggctgctat taacaagaga tggtggtaat aacaatgaca 1440 caaacgggac agagatcttc agacctgggg gaggagatat gagggacaat tggagaagtg 1500 aattatataa atataaagta gtgaaaattg aaccattagg agtagcaccc actaaggcaa 1560 agagaagagt ggtgcagaga gaaagaagag cagtgggaat aggagctttg ttccttgggt 1620 tcttgggagc agcaggaagc act 1643 <210> 26 <211> 494 <212> PRT <213> Human immunodeficiency virus type 1 <400> 26 Ser Ala Thr Glu Pro Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Arg Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Gly Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Ala Trp Glu Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Lys Cys Thr Asp Asn Leu Gly Asn Asp Thr Lys             100 105 110 Thr Ser Asn Lys Ser Trp Glu Lys Met Glu Pro Gly Glu Ile Lys Asn         115 120 125 Cys Ser Phe Asn Ile Thr Thr Ser Ile Gly Asp Lys Thr Gln Glu Thr     130 135 140 Tyr Ala Phe Phe Tyr Lys Leu Asp Val Val Pro Ile Asp Asn Lys Thr 145 150 155 160 Thr Ile Asp Asn Asn Thr Ala Arg Asn Tyr Ser Asp Tyr Arg Leu Ile                 165 170 175 Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe             180 185 190 Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu         195 200 205 Lys Cys Asn Asn Lys Thr Phe Met Gly Lys Gly Pro Cys Thr Asn Val     210 215 220 Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln 225 230 235 240 Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Ile Ile Ile Arg Ser                 245 250 255 Glu Asn Phe Thr Asp Asn Ala Lys Thr Leu Ile Ile His Leu Asn His             260 265 270 Ser Val Glu Ile Lys Cys Ile Arg Pro Asn Asn Asn Thr Ser Glu Gly         275 280 285 Ile His Ile Gly Pro Gly Arg Ala Phe Tyr Pro Thr Arg Ile Ile Gly     290 295 300 Asp Ile Arg Lys Ala His Cys Asn Ile Asn Glu Thr Ala Trp Lys Thr 305 310 315 320 Thr Leu Ala Gln Ile Val Thr Lys Leu Arg Glu Gln Phe Gly Asn Lys                 325 330 335 Thr Ile Val Phe Ser Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Met             340 345 350 His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asp Thr Thr Lys         355 360 365 Leu Phe Asn Ser Thr Trp Asn Val Asn Asp Thr Trp Asn Gly Ala Gly     370 375 380 Gly Ser Asn Ser Thr Glu Arg Asn Thr Thr Ile Ile Leu Pro Cys Lys 385 390 395 400 Ile Lys Gln Ile Ile Asn Leu Trp Gln Glu Val Gly Lys Ala Met Tyr                 405 410 415 Ala Pro Pro Ile Lys Gly Leu Ile Arg Cys Ser Ser Asn Ile Thr Gly             420 425 430 Leu Leu Leu Thr Arg Asp Gly Gly Asn Asn Asn Asp Thr Asn Gly Thr         435 440 445 Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser     450 455 460 Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val Ala 465 470 475 480 Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Arg Arg                 485 490 <210> 27 <211> 1613 <212> DNA <213> Human immunodeficiency virus type 1 <400> 27 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tgtcagctct 60 tgtggaaatg gggcaccatg ctccttggga tgttgatgat ctgtagtgct gcagaacaac 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga tgcaaccacc actttatttt 180 gtgcatcaga tgctaaagca tacgacaaag aggcacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccctaac ccacgagaaa taaaattgga aaatgtgaca gaaaatttta 300 acatgtggaa aaatgacatg gcagaccaga tgcatgagga tataatcagt ttatgggatc 360 aaagcctaaa gccatgtgta gaattaaccc cactctgtgt tactttaaat tgcactaata 420 ttagtttgaa tagtactaac aatgatacta ttaacagtag taatagtact gaaggaataa 480 atatgaggga agaaatgaaa aactgctctt tcaataccac cacaagtata ggagataaga 540 ataagagaga atatgcactt ttttataaac ttgatgtagt accaatagat aataagacaa 600 gctatacgtt gataaattgt aacacctcag tcattaaaca ggcctgtcca aaggtaacct 660 ttgaaccaat tcccatacat tattgtgccc cggctggttt tgcgattcta aagtgtctca 720 ataagacgtt cgatggaaat ggaacatgta caaatgtcag cacagtacag tgtacacatg 780 gcattagacc agtagtgtca acccaactac tgttaaatgg cagtctagca gaagaagagg 840 tagtaattag atatgagaat gtccaggaca atactaaaac cataatagta cagctgaacg 900 aaactgtaaa aattaattgt acaagaccca acaacaatac aagaaaaggt atacatgtgg 960 gatgggggag accaatttat gcaacaggag aaataatagg agatataaga caagcacatc 1020 gtaatctaag taaaaaagac tggggagaca ctttaaagaa gatagctata aaactacaag 1080 aacaatttaa tacaacaata atctttgagc aatcctcagg aggggaccca gaaattacaa 1140 tgcacagtct taattgtgga ggggaatttt tctactgtaa tacatcaaag ctgtttaatg 1200 gcacttggtc taatggtact tggactagtg gtatttggaa taatactgga gagtcagata 1260 gcacaatcac actcccatgc agaataaaac aaattataaa caggtggcag ggagtaggac 1320 aagcaatgta taaccctccc atcaacggac taattagctg ttcatcaaat attacaggac 1380 tgatattaac aagagatgga ggtaacaaca ggtccaacga gaccttcaga ccaagtggag 1440 gaaacatgag ggacaattgg agaagtgaat tatataaata tagagtagta aaaattgaac 1500 cattaggagt agcacccacc aaggcaaaga gaagagtggt gcagagagaa aaaagagcag 1560 tggggatgat aggagctgtg ttccttgggt tcttgggagc agcaggaagc act 1613 <210> 28 <211> 484 <212> PRT <213> Human immunodeficiency virus type 1 <400> 28 Ser Ala Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Asp Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Lys Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Arg Glu Ile Lys Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asp Met Ala Asp Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Glu Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asn Ile Ser Leu Asn Ser Thr Asn             100 105 110 Asn Asp Thr Ile Asn Ser Ser Asn Ser Thr Glu Gly Ile Asn Met Arg         115 120 125 Glu Glu Met Lys Asn Cys Ser Phe Asn Thr Thr Thr Ser Ile Gly Asp     130 135 140 Lys Asn Lys Arg Glu Tyr Ala Leu Phe Tyr Lys Leu Asp Val Val Pro 145 150 155 160 Ile Asp Asn Lys Thr Ser Tyr Thr Leu Ile Asn Cys Asn Thr Ser Val                 165 170 175 Ile Lys Gln Ala Cys Pro Lys Val Thr Phe Glu Pro Ile Pro Ile His             180 185 190 Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Leu Asn Lys Thr         195 200 205 Phe Asp Gly Asn Gly Thr Cys Thr Asn Val Ser Thr Val Gln Cys Thr     210 215 220 His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser 225 230 235 240 Leu Ala Glu Glu Glu Val Val Ile Arg Tyr Glu Asn Val Gln Asp Asn                 245 250 255 Thr Lys Thr Ile Ile Val Gln Leu Asn Glu Thr Val Lys Ile Asn Cys             260 265 270 Thr Arg Pro Asn Asn Asn Thr Arg Lys Gly Ile His Val Gly Trp Gly         275 280 285 Arg Pro Ile Tyr Ala Thr Gly Glu Ile Ile Gly Asp Ile Arg Gln Ala     290 295 300 His Arg Asn Leu Ser Lys Lys Asp Trp Gly Asp Thr Leu Lys Lys Ile 305 310 315 320 Ala Ile Lys Leu Gln Glu Gln Phe Asn Thr Thr Ile Ile Phe Glu Gln                 325 330 335 Ser Ser Gly Gly Asp Pro Glu Ile Thr Met His Ser Leu Asn Cys Gly             340 345 350 Gly Glu Phe Phe Tyr Cys Asn Thr Ser Lys Leu Phe Asn Gly Thr Trp         355 360 365 Ser Asn Gly Thr Trp Thr Ser Gly Ile Trp Asn Asn Thr Gly Glu Ser     370 375 380 Asp Ser Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Arg 385 390 395 400 Trp Gln Gly Val Gly Gln Ala Met Tyr Asn Pro Pro Ile Asn Gly Leu                 405 410 415 Ile Ser Cys Ser Ser Asn Ile Thr Gly Leu Ile Leu Thr Arg Asp Gly             420 425 430 Gly Asn Asn Arg Ser Asn Glu Thr Phe Arg Pro Ser Gly Gly Asn Met         435 440 445 Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Arg Val Val Lys Ile     450 455 460 Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln 465 470 475 480 Arg Glu Lys Arg                  <210> 29 <211> 1646 <212> DNA <213> Human immunodeficiency virus type 1 <400> 29 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaac tatcagcact 60 tgtggaaatg gggcaccttg ctccttggga tatcgatgat ctgtagtgct aaagaagaca 120 agttgtgggt cacagtctat tatggggtac ctgtgtggag agatgcaaac accactctat 180 tttgtgcatc aggtgctaaa gcatataaga cagaggtaca taatgtctgg gccacacatg 240 cctgtgtacc cacagacccc aacccacaag aagtggtatt gggaaatgtg acagaatatt 300 ttaatgcatg gaaaaatgac atggtagaac agatgcatga ggatataatc aatctatggg 360 atcaaagcct aaagccatgt gtaaaattaa ccccactctg tgtcacttta aattgcacta 420 acgttaaaaa caatgctacc aaaataaatg ataccaccac tacacctagt gaggaaatag 480 aaataaaaaa ctgctctttc aacatcaccg caggcataag agataagata cagaaagaat 540 atgcattgtt ttctaaattt gatttagtac aaatccatga agataataaa aataataata 600 atacaaacta tacagactat aggttgataa gttgtaacac ctcagtcatt acgcaggcct 660 gtccaaaagt atcctttgag ccaattccca tacatttttg taccccggct ggttttgcga 720 ttctaaagcg taataataag acattcaacg gaaaagggcc atgtacaaat gtcagtacag 780 tacagtgtac acatggaatt aggccagtag tatcaactca actgctgcta aatggcagtt 840 tagcagaaga ggatgtagta attagatctg aaaatttcac aaacaatgtt aaaaccataa 900 tagtacagct gaaagaagct gtacaaatta attgcacaag gcccaacaac aatacaagaa 960 aaagtatacc tataggacca gggagagcat tttatgcaac aggagacata ataggagata 1020 taagacaagc acattgtaac attagtggaa cacaatggaa taaaacttta ggaaagatag 1080 ttgaaaaatt aaaagaacaa tttgggaata aaacaataat ctttaaccaa cccgtaggag 1140 gggacccaga aattgtagcg cacactttta attgtggagg ggaatttttc tactgtaata 1200 caacacctct gtttaatagt acctggactt ggaatagtac ttggaatggt actacaagta 1260 ctgggaatgt tactaaaaaa attatcacac tccaatgcag aataagacaa attgtaaaca 1320 tgtggcagaa agtaggaaaa gcaatgtatg cccctcccat cagaggacag attggatgtt 1380 catcaaatat tacagggctg ctattaacaa gagatggtgg taatagtgag aacgggacca 1440 ataacacaga cacagagacc ttcagaccgg gaggaggaga tatgagggac aattggagaa 1500 gtgaattata taaatataaa gtagtaagaa ttgaaccatt aggaatagca cccactaagg 1560 caaggagaag agtggtgcag agagaaaaaa gagcagtggg aataggggct ttgttccttg 1620 ggttcttggg agcagcagga agcact 1646 <210> 30 <211> 496 <212> PRT <213> Human immunodeficiency virus type 1 <400> 30 Ser Ala Lys Glu Asp Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro 1 5 10 15 Val Trp Arg Asp Ala Asn Thr Thr Leu Phe Cys Ala Ser Gly Ala Lys             20 25 30 Ala Tyr Lys Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val         35 40 45 Pro Thr Asp Pro Asn Pro Gln Glu Val Val Leu Gly Asn Val Thr Glu     50 55 60 Tyr Phe Asn Ala Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp 65 70 75 80 Ile Ile Asn Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr                 85 90 95 Pro Leu Cys Val Thr Leu Asn Cys Thr Asn Val Lys Asn Asn Ala Thr             100 105 110 Lys Ile Asn Asp Thr Thr Thr Thr Pro Ser Glu Glu Ile Glu Ile Lys         115 120 125 Asn Cys Ser Phe Asn Ile Thr Ala Gly Ile Arg Asp Lys Ile Gln Lys     130 135 140 Glu Tyr Ala Leu Phe Ser Lys Phe Asp Leu Val Gln Ile His Glu Asp 145 150 155 160 Asn Lys Asn Asn Asn Asn Thr Asn Tyr Thr Asp Tyr Arg Leu Ile Ser                 165 170 175 Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu             180 185 190 Pro Ile Pro Ile His Phe Cys Thr Pro Ala Gly Phe Ala Ile Leu Lys         195 200 205 Arg Asn Asn Lys Thr Phe Asn Gly Lys Gly Pro Cys Thr Asn Val Ser     210 215 220 Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu 225 230 235 240 Leu Leu Asn Gly Ser Leu Ala Glu Glu Asp Val Val Ile Arg Ser Glu                 245 250 255 Asn Phe Thr Asn Asn Val Lys Thr Ile Ile Val Gln Leu Lys Glu Ala             260 265 270 Val Gln Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile         275 280 285 Pro Ile Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly     290 295 300 Asp Ile Arg Gln Ala His Cys Asn Ile Ser Gly Thr Gln Trp Asn Lys 305 310 315 320 Thr Leu Gly Lys Ile Val Glu Lys Leu Lys Glu Gln Phe Gly Asn Lys                 325 330 335 Thr Ile Ile Phe Asn Gln Pro Val Gly Gly Asp Pro Glu Ile Val Ala             340 345 350 His Thr Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Thr Pro         355 360 365 Leu Phe Asn Ser Thr Trp Thr Trp Asn Ser Thr Trp Asn Gly Thr Thr     370 375 380 Ser Thr Gly Asn Val Thr Lys Lys Ile Ile Thr Leu Gln Cys Arg Ile 385 390 395 400 Arg Gln Ile Val Asn Met Trp Gln Lys Val Gly Lys Ala Met Tyr Ala                 405 410 415 Pro Pro Ile Arg Gly Gln Ile Gly Cys Ser Ser Asn Ile Thr Gly Leu             420 425 430 Leu Leu Thr Arg Asp Gly Gly Asn Ser Glu Asn Gly Thr Asn Asn Thr         435 440 445 Asp Thr Glu Thr Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp     450 455 460 Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Pro Leu Gly 465 470 475 480 Ile Ala Pro Thr Lys Ala Arg Arg Arg Val Val Gln Arg Glu Lys Arg                 485 490 495 <210> 31 <211> 1606 <212> DNA <213> Human immunodeficiency virus type 1 <400> 31 agaaagacag aagacagtgg caatgagagc gaaggggacc aggaagaatt gtcagcactt 60 gtggtggaga tggggcacca tgctctttgg gatgttgatg atctgtagtg ctgcaaaaga 120 aaaattgtgg gtcacagtct attatggggt gcctgtgtgg aaagaagcaa ccaccactct 180 attttgtgca tcagatgcta aagcatatga cacagaagca cataatgttt gggccacaca 240 tgcttgtgta cccacaaacc ctaacccaca agaagtatta ttgaaaaatg tgacagaaga 300 ttttaacatg tggaaaaata atatggtaga acagatgcat gaggatataa tcagtttatg 360 ggatcaaagc ctaaagccat gtgtgaaatt aaccccactc tgtgttactt tacattgcac 420 tgatgcgaac attactgcaa acagtactgc tactaacagt actgttagct ccattaaaga 480 agaagtgaaa aactgctctt tcaatatcac cacagaagta agagacaagg taaagaaaga 540 acatgcactt ttttatagac ttgatgtagt accaatagct aatgataata caagctatac 600 attggtaaat tgtaacacct caaccattac acaggcctgt ccaaaggtga cctttgaacc 660 aattcctata cattattgtg ccccggctgg ttttgcgatt ctaaaatgta atgataagaa 720 tttcaatgga acaggaccat gtaaaaatgt cagcacagta caatgcacac atggaattag 780 gccagtggtg tcaactcaac tactgttaaa tggcagtcta gcagaagatg aggtagtaat 840 tagatctgaa aatttcacaa acaatgcaaa aatcataata gtacagctaa atgaatctgt 900 aataattaat tatacaagac ctggcaacaa tacaagaaaa agtatacata taggaccggg 960 aagtgcattt tatgcaacag gagacataat aggagatata agacaagcac attgtaacat 1020 tagtaaagca gattgggaga aaacactaaa acaggtagtt aaaaaattac aggaacaata 1080 tgggaataaa acaataaact ttacccaatc ctcaggagga gacccagaaa ttgtaatgca 1140 cagtcttaat tgtggaggag aatttttcta ttgtaataca acaaagctgt ttaatagtac 1200 ttggcagaat ggtactattg taggatcaga aaatacgtca gacattatca tactcccatg 1260 cagaataaag caaattataa acaggtggca ggaagtagga aaagcaatgt atgcccctcc 1320 catcagcgga gacattagat gtacatcaaa tattacaggg ctgctattaa caagagatgg 1380 gggtataaag aacaagacca atgggacaga gacagagatc ttcagacctg caggaggaga 1440 tatgaaggac aattggagaa gtgaattata taaatataaa gtagtaaaaa ttgaaccgtt 1500 aggaatagca cccaccaggg caaggagaag agtggtgcag agggaaaaaa gagaagtgac 1560 gctgggagtt atgttccttg ggttcttggg agcagcagga agcact 1606 <210> 32 <211> 482 <212> PRT <213> Human immunodeficiency virus type 1 <400> 32 Ser Ala Ala Lys Glu Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro 1 5 10 15 Val Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys             20 25 30 Ala Tyr Asp Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val         35 40 45 Pro Thr Asn Pro Asn Pro Gln Glu Val Leu Leu Lys Asn Val Thr Glu     50 55 60 Asp Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp 65 70 75 80 Ile Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr                 85 90 95 Pro Leu Cys Val Thr Leu His Cys Thr Asp Ala Asn Ile Thr Ala Asn             100 105 110 Ser Thr Ala Thr Asn Ser Thr Val Ser Ser Ile Lys Glu Glu Val Lys         115 120 125 Asn Cys Ser Phe Asn Ile Thr Thr Glu Val Arg Asp Lys Val Lys Lys     130 135 140 Glu His Ala Leu Phe Tyr Arg Leu Asp Val Val Pro Ile Ala Asn Asp 145 150 155 160 Asn Thr Ser Tyr Thr Leu Val Asn Cys Asn Thr Ser Thr Ile Thr Gln                 165 170 175 Ala Cys Pro Lys Val Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala             180 185 190 Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Asn Phe Asn Gly         195 200 205 Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile     210 215 220 Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu 225 230 235 240 Asp Glu Val Val Ile Arg Ser Glu Asn Phe Thr Asn Asn Ala Lys Ile                 245 250 255 Ile Ile Val Gln Leu Asn Glu Ser Val Ile Ile Asn Tyr Thr Arg Pro             260 265 270 Gly Asn Asn Thr Arg Lys Ser Ile His Ile Gly Pro Gly Ser Ala Phe         275 280 285 Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn     290 295 300 Ile Ser Lys Ala Asp Trp Glu Lys Thr Leu Lys Gln Val Val Lys Lys 305 310 315 320 Leu Gln Glu Gln Tyr Gly Asn Lys Thr Ile Asn Phe Thr Gln Ser Ser                 325 330 335 Gly Gly Asp Pro Glu Ile Val Met His Ser Leu Asn Cys Gly Gly Glu             340 345 350 Phe Phe Tyr Cys Asn Thr Thr Lys Leu Phe Asn Ser Thr Trp Gln Asn         355 360 365 Gly Thr Ile Val Gly Ser Glu Asn Thr Ser Asp Ile Ile Ile Leu Pro     370 375 380 Cys Arg Ile Lys Gln Ile Ile Asn Arg Trp Gln Glu Val Gly Lys Ala 385 390 395 400 Met Tyr Ala Pro Pro Ile Ser Gly Asp Ile Arg Cys Thr Ser Asn Ile                 405 410 415 Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Ile Lys Asn Lys Thr Asn             420 425 430 Gly Thr Glu Thr Glu Ile Phe Arg Pro Ala Gly Gly Asp Met Lys Asp         435 440 445 Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro     450 455 460 Leu Gly Ile Ala Pro Thr Arg Ala Arg Arg Arg Val Val Gln Arg Glu 465 470 475 480 Lys arg          <210> 33 <211> 1589 <212> DNA <213> Human immunodeficiency virus type 1 <400> 33 agaaagagca gaagacagtg gcaatgaaag tgaaggggac caggaagagt tatcagcact 60 tgtggagatg gggcatcatg ccccttggga tgttgacgat ttgtagtgtt gcagaacaat 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga agccaccacc actctatttt 180 gtgcatcaga agctaaggca tatgttacag aggtacataa tatttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaag cagtattgga aaatgtgaca gaaaatttta 300 acatatggaa aaatgacatg gtagaccaga tgcatgagga tataatcagt gtatgggatc 360 aaagcctaaa gccatgtgtg aaattaaccc cgctctgtgt cactttaaat tgcactgatt 420 attttgggaa aactaatatt actaccactt ctagcagtgg tcccaataat gatagaggaa 480 tgaaaaactg ctctttcaat atcaccacaa gcataagaga taaggtaacg aaagaacatg 540 cactttttta tagagttgat gtagtcccaa tagatagtag taatagtagc tatagattga 600 taaattgtaa cacctcagtc attacacagg ccagtccaaa agtatccttt gagccaattc 660 ccatacatta ttgtaccccg gctggttttg cgattataaa gtgtaataat aagacattca 720 atggaacagg accatgtaga aatgtcagca cagtacaatg tacacatgga attaggccaa 780 tagtgtcaac tcagctgttg ttaaatggca gtctagcagt agaagaggta gtaattagat 840 ctgaaaatat cacgaacaat gctaaaacca taatagtaca attgaacgaa tctgtaagca 900 tcaattgtac aagacccagc aacaatacaa gaagggggat acatatggga ccagggagag 960 cattttggac aacaggtgaa gtaataggag atataaggaa agcacattgt aacattagta 1020 gaaaagaatg gaatgacact ttagacaagg tagtcaaaaa attaagggaa aaatttaatg 1080 caacaataat ctttaatcaa tccacaggag gggacccaga aattgtaatg cacactttta 1140 attgtggagg ggagtttttc tactgtaaca catcacaact gtttaatagt acttgggata 1200 ttaatggaaa tactactgga gggttagaag gcaatgacac aatcacactc caatgtagaa 1260 taaaacaaat tgtaaacatg tggcaggaag taggaaaagc aatgtatgcc cctcccatcc 1320 aaggaaaaat tagatgttca tcaaatatta cagggctgct attaacaaga gatggtggta 1380 ataacagtag taacaatgag accttcagac ctggaggagg agatatgagg gacaattgga 1440 gaagtgaact atataaatat aaagtagtaa aaattcaacc actaggaata gcacccacca 1500 aggcaaagag aagagtggtg cagagagaaa aaagagcagt gggaatagga gctttgttcc 1560 ttgggttctt gggagcagca ggaagcact 1589 <210> 34 <211> 477 <212> PRT <213> Human immunodeficiency virus type 1 <400> 34 Ser Val Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Glu Ala Lys Ala             20 25 30 Tyr Val Thr Glu Val His Asn Ile Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Ala Val Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Ile Trp Lys Asn Asp Met Val Asp Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Val Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Tyr Phe Gly Lys Thr Asn Ile             100 105 110 Thr Thr Thr Ser Ser Ser Gly Pro Asn Asn Asp Arg Gly Met Lys Asn         115 120 125 Cys Ser Phe Asn Ile Thr Thr Ser Ile Arg Asp Lys Val Thr Lys Glu     130 135 140 His Ala Leu Phe Tyr Arg Val Asp Val Val Pro Ile Asp Ser Ser Asn 145 150 155 160 Ser Ser Tyr Arg Leu Ile Asn Cys Asn Thr Ser Val Ile Thr Gln Ala                 165 170 175 Ser Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Thr Pro             180 185 190 Ala Gly Phe Ala Ile Ile Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr         195 200 205 Gly Pro Cys Arg Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg     210 215 220 Pro Ile Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Val Glu 225 230 235 240 Glu Val Val Ile Arg Ser Glu Asn Ile Thr Asn Asn Ala Lys Thr Ile                 245 250 255 Ile Val Gln Leu Asn Glu Ser Val Ser Ile Asn Cys Thr Arg Pro Ser             260 265 270 Asn Asn Thr Arg Arg Gly Ile His Met Gly Pro Gly Arg Ala Phe Trp         275 280 285 Thr Thr Gly Glu Val Ile Gly Asp Ile Arg Lys Ala His Cys Asn Ile     290 295 300 Ser Arg Lys Glu Trp Asn Asp Thr Leu Asp Lys Val Val Lys Lys Leu 305 310 315 320 Arg Glu Lys Phe Asn Ala Thr Ile Ile Phe Asn Gln Ser Thr Gly Gly                 325 330 335 Asp Pro Glu Ile Val Met His Thr Phe Asn Cys Gly Gly Glu Phe Phe             340 345 350 Tyr Cys Asn Thr Ser Gln Leu Phe Asn Ser Thr Trp Asp Ile Asn Gly         355 360 365 Asn Thr Thr Gly Gly Leu Glu Gly Asn Asp Thr Ile Thr Leu Gln Cys     370 375 380 Arg Ile Lys Gln Ile Val Asn Met Trp Gln Glu Val Gly Lys Ala Met 385 390 395 400 Tyr Ala Pro Pro Ile Gln Gly Lys Ile Arg Cys Ser Ser Asn Ile Thr                 405 410 415 Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Asn Ser Ser Asn Asn Glu             420 425 430 Thr Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu         435 440 445 Leu Tyr Lys Tyr Lys Val Val Lys Ile Gln Pro Leu Gly Ile Ala Pro     450 455 460 Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg 465 470 475 <210> 35 <211> 1703 <212> DNA <213> Human immunodeficiency virus type 1 <400> 35 agaaagagca gaagacagtg gcaatgagag tgagggagac caggaagaat tatcagcact 60 tgtggagatg gggcaacata tggagatggg gcatgatgct ccttgggatg ttgatgatct 120 gtagtgctgc agaagatttg tgggtcacag tttattatgg ggtacctgtg tggaaagacg 180 caaagaccac tctattttgt gcatcagatg ctaaagcata taagacagag gtacataatg 240 tttgggccac gcatgcctgt gtacccacag accccaaccc acaagaagta gaaatgaaaa 300 atgtgacaga agattttaac atgtggaaaa ataatatggt agaacagatg catgaggata 360 taatcagttt atgggatcag agcctaaaac cacgtgtaaa attaacccca ctctgtgtta 420 ctttaaagtg ctttgatgtg aagaataaaa ccactactac cactactaat agtaccacat 480 ccactattag tactactacc actaagacgc ccactgttag taaagggaca gagaaatcag 540 aactgacaaa ctgctctttc aatatcacca caaacataag agataagttt cagaaaaact 600 atgcaatttt tgataaactt gatgtagtac caatagatga tgataatgat actactacta 660 acaataatac tagtaatgaa aaaagcttta ggttaataaa ttgtaacacc tcagtcatca 720 cacaggcctg cccaaagata tcatttgaac caattcccat acattattgt accccggctg 780 gttttgcgat tctaaagtgt aaagataaaa atttcaatgg aacaggaaaa tgtaaaagcg 840 tcagcacagt gcaatgtaca catggaatta ggccagtagt gtcaactcaa ctactgttaa 900 atggcagtct agcagaagaa gaggtagtaa ttagatctgc cgatttctcg gacaatacta 960 aaatcataat agtacagctg aataaatctg tagaaattaa ttgtacaaga cccaacaaca 1020 ataaaagaaa aagtataaat ataggaccag ggagagcaat gtttgcaaca ggagacataa 1080 taggagatat aagaaaagca tcttgtacca ttaatgaaac acaatggaat aacacgttac 1140 aacaggtagt tataaaatta aaagaacaat atggaaataa aacaatagtc tttgaccgcc 1200 cctcaggagg ggacccagaa attgtaatgc acagttttaa ttgtggagga gaatttttct 1260 attgtaattc aacacaactg tttaatagta gttgggggcc taatggtact cggaatggta 1320 ctacaacgat aaatggtact atcatactcc catgtagaat aaaacaaatt ataaacatgt 1380 ggcaggaagt aggaaaagca atgtatgccc ctcccatcga gggacttatt aactgtacat 1440 caaatatcac agggctacta ttaacaagag atggtggcca tgacaataat gacacaaaaa 1500 ataacaatac cgagatcttc agacctggag gaggagatat gagggacaat tggagaagtg 1560 aattatataa atataaagta gtaaaaattg aaccattagg aatagcaccc aacaggacaa 1620 aaagaatagt ggtgcaaaga gaaaaaagag cagtgggatt cggagctgtg ttccttgggt 1680 tcttgggagc agcaggaagc act 1703 <210> 36 <211> 509 <212> PRT <213> Human immunodeficiency virus type 1 <400> 36 Ser Ala Ala Glu Asp Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Asp Ala Lys Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Lys Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Glu Met Lys Asn Val Thr Glu Asp     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Arg Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Lys Cys Phe Asp Val Lys Asn Lys Thr Thr Thr             100 105 110 Thr Thr Thr Asn Ser Thr Thr Ser Ser Thr Ile Ser Thr Thr Thr Thr Lys         115 120 125 Thr Pro Thr Val Ser Lys Gly Thr Glu Lys Ser Glu Leu Thr Asn Cys     130 135 140 Ser Phe Asn Ile Thr Thr Asn Ile Arg Asp Lys Phe Gln Lys Asn Tyr 145 150 155 160 Ala Ile Phe Asp Lys Leu Asp Val Val Pro Ile Asp Asp Asp Asn Asp                 165 170 175 Thr Thr Thr Asn Asn Asn Thr Ser Asn Glu Lys Ser Phe Arg Leu Ile             180 185 190 Asn Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Ile Ser Phe         195 200 205 Glu Pro Ile Pro Ile His Tyr Cys Thr Pro Ala Gly Phe Ala Ile Leu     210 215 220 Lys Cys Lys Asp Lys Asn Phe Asn Gly Thr Gly Lys Cys Lys Ser Val 225 230 235 240 Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln                 245 250 255 Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser             260 265 270 Ala Asp Phe Ser Asp Asn Thr Lys Ile Ile Ile Val Gln Leu Asn Lys         275 280 285 Ser Val Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Lys Arg Lys Ser     290 295 300 Ile Asn Ile Gly Pro Gly Arg Ala Met Phe Ala Thr Gly Asp Ile Ile 305 310 315 320 Gly Asp Ile Arg Lys Ala Ser Cys Thr Ile Asn Glu Thr Gln Trp Asn                 325 330 335 Asn Thr Leu Gln Gln Val Val Ile Lys Leu Lys Glu Gln Tyr Gly Asn             340 345 350 Lys Thr Ile Val Phe Asp Arg Pro Ser Gly Gly Asp Pro Glu Ile Val         355 360 365 Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr     370 375 380 Gln Leu Phe Asn Ser Ser Trp Gly Pro Asn Gly Thr Arg Asn Gly Thr 385 390 395 400 Thr Thr Ile Asn Gly Thr Ile Ile Leu Pro Cys Arg Ile Lys Gln Ile                 405 410 415 Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile             420 425 430 Glu Gly Leu Ile Asn Cys Thr Ser Asn Ile Thr Gly Leu Leu Leu Thr         435 440 445 Arg Asp Gly Gly His Asp Asn Asn Asp Thr Lys Asn Asn Asn Thr Glu     450 455 460 Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu 465 470 475 480 Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Ile Ala Pro                 485 490 495 Asn Arg Thr Lys Arg Ile Val Val Gln Arg Glu Lys Arg             500 505 <210> 37 <211> 1658 <212> DNA <213> Human immunodeficiency virus type 1 <400> 37 agaaagagca gaagacagtg gcaatgaaag tgaaggggat caagaagagt tatcagcact 60 tgttgagatg gggcgccatg ctccttggga tgttaatgat ctgtagtgct gcagaacaat 120 tgtgggtcac agtctattat ggggtacctg tgtggagaga agcaaacacc actctatttt 180 gtgcatcaga tgctaaagca tatgataaag aggtacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaag tagaattgga aaatgtgaca gaaaatttta 300 acatgtggaa aaatgacatg gtagaacaga tgcatgagga tataatcagt ttatgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cactctgcgt tactttaaat tgtactgatt 420 taaggtcaca gaatgtgact tataccactg gtgctaatac cactatggct actaccacta 480 gtactaatac cactagtagt gggggagaga tgcaggtagg aatgaaaaac tgctctttca 540 atatcaccac aaacacacaa gataaggtga agggatatgc acattttgat aaccttgatc 600 tagtacaaat agaggatgaa aatcacagca ataacagcta taggttgata cattgtaaca 660 cctcagtaat tacacaggcc tgtccaaagg tatcctttga gccaattcct atacattatc 720 gtgccccggc tggttttgcg attctaaagt gtaaagataa gaagttcaat ggaacaggac 780 cctgtacaaa tgtcagcaca gtacagtgta cacatggaat taggccagta gtatccactc 840 aactgctgtt caatggcagt ctagcagaag aagaggtagt aattagatct gccaatttct 900 cagaaaatga taaaatcata atagtacagc tgaaagacgc tgtacaaatt aattgtacaa 960 gacccaacaa caacaccaga aaaggtatac atatgggacc agggaaagta ttttacgcaa 1020 cagaagtcat aggggacata aggcgagcac attgtaacat tagtaaagaa aattggaata 1080 atactttaaa acagatagct atacaattaa gagagcaaga gcagttcaag aataaaacaa 1140 tagtctttaa tcaatcctca ggaggggacc cagaaattgt aatgtctagt tttaattgtg 1200 gaggggaatt tttctactgt aatacaacac aactgtttaa tagtacttgg gagaatgata 1260 ctagtacttg gaatgatact gaagggtcga atggcactat cacactccca tgcagaataa 1320 aacaaattat caacatgtgg caggaggtag gaaaagcaat atatgcccct cccatcaaag 1380 gaccacttca ttgttcatca aatattacag ggctactatt aacaagagat ggtggtaata 1440 ctaatgagag caacaccacc gaggtcgagg tcttcagacc tttaggagga aacatgaggg 1500 acaattggag aagtgaatta tataaatata aagtagtaaa gattgaacca ttaggaatag 1560 cacccaccaa ggcaaagaga agagtggtgc agagagaaaa aagagcagtg ggaataggag 1620 ctgtgttcct tgggttcttg ggagcagcag gaagcact 1658 <210> 38 <211> 500 <212> PRT <213> Human immunodeficiency virus type 1 <400> 38 Ser Ala Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Arg Glu Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Lys Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Glu Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Leu Arg Ser Gln Asn Val Thr             100 105 110 Tyr Thr Thr Gly Ala Asn Thr Thr Met Ala Thr Thr Thr Ser Thr Asn         115 120 125 Thr Thr Ser Ser Gly Gly Glu Met Gln Val Gly Met Lys Asn Cys Ser     130 135 140 Phe Asn Ile Thr Thr Asn Thr Gln Asp Lys Val Lys Gly Tyr Ala His 145 150 155 160 Phe Asp Asn Leu Asp Leu Val Gln Ile Glu Asp Glu Asn His Ser Asn                 165 170 175 Asn Ser Tyr Arg Leu Ile His Cys Asn Thr Ser Val Ile Thr Gln Ala             180 185 190 Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Arg Ala Pro         195 200 205 Ala Gly Phe Ala Ile Leu Lys Cys Lys Asp Lys Lys Phe Asn Gly Thr     210 215 220 Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg 225 230 235 240 Pro Val Val Ser Thr Gln Leu Leu Phe Asn Gly Ser Leu Ala Glu Glu                 245 250 255 Glu Val Val Ile Arg Ser Ala Asn Phe Ser Glu Asn Asp Lys Ile Ile             260 265 270 Ile Val Gln Leu Lys Asp Ala Val Gln Ile Asn Cys Thr Arg Pro Asn         275 280 285 Asn Asn Thr Arg Lys Gly Ile His Met Gly Pro Gly Lys Val Phe Tyr     290 295 300 Ala Thr Glu Val Ile Gly Asp Ile Arg Arg Ala His Cys Asn Ile Ser 305 310 315 320 Lys Glu Asn Trp Asn Asn Thr Leu Lys Gln Ile Ala Ile Gln Leu Arg                 325 330 335 Glu Gln Glu Gln Phe Lys Asn Lys Thr Ile Val Phe Asn Gln Ser Ser             340 345 350 Gly Gly Asp Pro Glu Ile Val Met Ser Ser Phe Asn Cys Gly Gly Glu         355 360 365 Phe Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn Ser Thr Trp Glu Asn     370 375 380 Asp Thr Ser Thr Trp Asn Asp Thr Glu Gly Ser Asn Gly Thr Ile Thr 385 390 395 400 Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly                 405 410 415 Lys Ala Ile Tyr Ala Pro Pro Ile Lys Gly Pro Leu His Cys Ser Ser             420 425 430 Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Thr Asn Glu         435 440 445 Ser Asn Thr Thr Glu Val Glu Val Phe Arg Pro Leu Gly Gly Asn Met     450 455 460 Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile 465 470 475 480 Glu Pro Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln                 485 490 495 Arg Glu Lys Arg             500 <210> 39 <211> 1568 <212> DNA <213> Human immunodeficiency virus type 1 <400> 39 agaaagagca gaagacagtg gcaatgagag tgaaggggat catgaagaat tgtcagcact 60 tgtggtggag atggggcatg atgctccttg ggatgttgat gatctgtagt gctacagaac 120 aattgtgggt cacagtctat tatggggtac ctgtgtggaa agaagcaacc accactctat 180 tttgtgcatc agatgctaaa gcatatgaca cagaggcaca taatgtttgg gccacacatg 240 cctgtgtacc cacagaccct aacccacaag aagtagaatt gaaaaatgtg acagaaaatc 300 ttaacatgtg gaaaaatgac atggtagaac agatgcatga ggatataatc aatttatggg 360 atcaaagcct aaagccatgt gtaaaattaa ctccactctg tgtcacttta cattgcacta 420 atttgaatgt tactaccagt aatactacaa gttggggaga gatggaggca ggagaaataa 480 aaaactgctc tttcaatgtc accacacgca gaagaaataa gaaagaatat gcactttttt 540 ataaacttga tgtagtacct atagatagtg ataatgcaag ctatacgttg ataaattgta 600 acacttcagt cattacacaa gcctgtccaa aggtatcctt tgaaccaatt cccatacatt 660 attgtgcccc ggctggtttt gcgattctaa aatgtaatga taagaaattc aatggaacag 720 gaccatgtaa aaatgttagc acagtacaat gtacacatgg aattaggcca gtagtgtcaa 780 ttcaactgct gttaaatggc agtctagcag aagaagaggt agtaattaga tctgaaaatt 840 tctcgaacaa tgctaaagcc gtaatagtac agctgaatgc atctatagaa attaattgta 900 caagacccaa caacaataca agaaaagata tacatatagg accagggaga gcattatata 960 caacaggagg aataatagga gatataagac aagcacattg tagccttagg aaagcagaat 1020 ggaatgacac tttaaaacat gtagttacaa aattaagaga acaatttggg aataaaacaa 1080 tattctttaa tcaatcctca ggaggggacc cagagattgt aatgcacagt tttaattgtg 1140 gaggggaatt tttctactgt aatacaacaa tgctgtttaa tagtaatagt acttggaatg 1200 atactacagg accagataat aacactatca tactcccatg tagaataaaa caaattataa 1260 acaggtggca ggaagtagga aaagcaatgt atgcccctcc tatcagtgga ccaattaaac 1320 gcacatcaaa tattacaggg ctactattaa caagagatgg tggtagtaac accaccgaga 1380 ccttcagacc tggaggagga gatatgaggg acaattggag aagtgaatta tataaatata 1440 aagtagtaaa aattgagcca ttaggggtag cacccaccag ggcaaggaga agagtggtgc 1500 agagagaaaa aagagcagtg ggactgggag ctgtattcct tgggttcttg ggagcagcag 1560 gaagcact 1568 <210> 40 <211> 469 <212> PRT <213> Human immunodeficiency virus type 1 <400> 40 Ser Ala Thr Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Glu Leu Lys Asn Val Thr Glu Asn     50 55 60 Leu Asn Met Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Asn Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu His Cys Thr Asn Leu Asn Val Thr Thr Ser Asn             100 105 110 Thr Thr Ser Trp Gly Glu Met Glu Ala Gly Glu Ile Lys Asn Cys Ser         115 120 125 Phe Asn Val Thr Thr Arg Arg Arg Asn Lys Lys Glu Tyr Ala Leu Phe     130 135 140 Tyr Lys Leu Asp Val Val Pro Ile Asp Ser Asp Asn Ala Ser Tyr Thr 145 150 155 160 Leu Ile Asn Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val                 165 170 175 Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala             180 185 190 Ile Leu Lys Cys Asn Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Lys         195 200 205 Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser     210 215 220 Ile Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile 225 230 235 240 Arg Ser Glu Asn Phe Ser Asn Asn Ala Lys Ala Val Ile Val Gln Leu                 245 250 255 Asn Ala Ser Ile Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg             260 265 270 Lys Asp Ile His Ile Gly Pro Gly Arg Ala Leu Tyr Thr Thr Gly Gly         275 280 285 Ile Ile Gly Asp Ile Arg Gln Ala His Cys Ser Leu Arg Lys Ala Glu     290 295 300 Trp Asn Asp Thr Leu Lys His Val Val Thr Lys Leu Arg Glu Gln Phe 305 310 315 320 Gly Asn Lys Thr Ile Phe Phe Asn Gln Ser Ser Gly Gly Asp Pro Glu                 325 330 335 Ile Val Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn             340 345 350 Thr Thr Met Leu Phe Asn Ser Asn Ser Thr Trp Asn Asp Thr Thr Gly         355 360 365 Pro Asp Asn Asn Thr Ile Ile Leu Pro Cys Arg Ile Lys Gln Ile Ile     370 375 380 Asn Arg Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser 385 390 395 400 Gly Pro Ile Lys Arg Thr Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg                 405 410 415 Asp Gly Gly Ser Asn Thr Thr Glu Thr Phe Arg Pro Gly Gly Gly Asp             420 425 430 Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys         435 440 445 Ile Glu Pro Leu Gly Val Ala Pro Thr Arg Ala Arg Arg Arg Val Val     450 455 460 Gln Arg Glu Lys Arg 465 <210> 41 <211> 1541 <212> DNA <213> Human immunodeficiency virus type 1 <400> 41 agaaagagca gaagacagtg gcaatgagag tgaaggagat gaggaagcac tggcagcact 60 ggtggacagg gggcatcatg ctccttggga tgctgatgat ctgtagtgct gtaaacaact 120 tgtgggtcac tgtatattat ggagtgcctg tgtggagaga agcaaccacc accctatttt 180 gtgcatcaga tgctaaagca tacaaaacag aggtacataa tgtctgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaga tagatttggt aaatgtgaca gaaaatttta 300 acatgtggaa aaataacatg gtagaacaga tgcatgagga tataatcagt ttatgggatc 360 aaagcctaaa accatgcgta aaattaaccc cactctgtgt tgtgaaaaac tgctctttca 420 acaccaccac aatggtaagg gatagggagc ggaaagaata tgctctcttt tataaacttg 480 atgtagtaca aatgaatgat aataataata atagtaccca tggaacctat agattgataa 540 attgtaatac ctcagtcatt acacaggcct gtccaaaggt atcctttgag ccaattccca 600 tacattattg cgccccggct ggttttgcga ttctaaagtg taaagacaag aagttcaatg 660 gaacgggacc atgcaaaaat gtcagcacag tacagtgtac acatggaatt aggccagtag 720 tgtcaactca actgctgcta aatggcagtc tagcagaaga agaggtaata attagatctg 780 aaaacttcac aagcaatgct aaaaccataa tagtacagct aaatgaaact gtagagatta 840 attgcacaag acctagcaac aatacaagaa gaagtataca tataggacca gggagagcat 900 tttacacaac aggagacata ataggagata taagaaaagc acattgtaac attagtagaa 960 caaaatggaa taacacttta ggacagatag ttgaaaaatt acaagaacaa tttaagaata 1020 aaacaataat ctttaattca tcctcaggag gggacccaga aattgtatat cacagtttta 1080 attgtggagg ggaatttttc tactgtaata caacagaact gttcgatagt acctggtata 1140 gcccctggaa cagtactggt gggtcaaata acactgaagg gaatagcacg atcacactca 1200 aatgcagaat aaagcaaatt gtaaacaggt ggcaggaagt aggaaaagca atgtatgccc 1260 ctcccatcca gggaaaaatt aaatgttcat caaatattac agggctacta ttaacaagag 1320 acggtggtaa tagtaatagt agtaacgaga ccttcagacc aggaggagga gacatgagag 1380 acaattggag aagtgaatta tataaatata aagtaataaa aattgaacca ttaggagtag 1440 cacccaccaa ggcaaagaga agagtggtgc aaagagaaag aagagcagtg ggaacaatag 1500 gagctatgtt ccttgggttc ttgggagcag caggaagcac t 1541 <210> 42 <211> 460 <212> PRT <213> Human immunodeficiency virus type 1 <400> 42 Ser Ala Val Asn Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Arg Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Lys Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Ile Asp Leu Val Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Val Lys Asn Cys Ser Phe Asn Thr Thr Thr Met Val Arg             100 105 110 Asp Arg Glu Arg Lys Glu Tyr Ala Leu Phe Tyr Lys Leu Asp Val Val         115 120 125 Gln Met Asn Asp Asn Asn Asn Asn Ser Thr His Gly Thr Tyr Arg Leu     130 135 140 Ile Asn Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser 145 150 155 160 Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile                 165 170 175 Leu Lys Cys Lys Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn             180 185 190 Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr         195 200 205 Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Ile Ile Arg     210 215 220 Ser Glu Asn Phe Thr Ser Asn Ala Lys Thr Ile Ile Val Gln Leu Asn 225 230 235 240 Glu Thr Val Glu Ile Asn Cys Thr Arg Pro Ser Asn Asn Thr Arg Arg                 245 250 255 Ser Ile His Ile Gly Pro Gly Arg Ala Phe Tyr Thr Thr Gly Asp Ile             260 265 270 Ile Gly Asp Ile Arg Lys Ala His Cys Asn Ile Ser Arg Thr Lys Trp         275 280 285 Asn Asn Thr Leu Gly Gln Ile Val Glu Lys Leu Gln Glu Gln Phe Lys     290 295 300 Asn Lys Thr Ile Ile Phe Asn Ser Ser Ser Gly Gly Asp Pro Glu Ile 305 310 315 320 Val Tyr His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr                 325 330 335 Thr Glu Leu Phe Asp Ser Thr Trp Tyr Ser Pro Trp Asn Ser Thr Gly             340 345 350 Gly Ser Asn Asn Thr Glu Gly Asn Ser Thr Ile Thr Leu Lys Cys Arg         355 360 365 Ile Lys Gln Ile Val Asn Arg Trp Gln Glu Val Gly Lys Ala Met Tyr     370 375 380 Ala Pro Pro Ile Gln Gly Lys Ile Lys Cys Ser Ser Asn Ile Thr Gly 385 390 395 400 Leu Leu Leu Thr Arg Asp Gly Gly Asn Ser Asn Ser Ser Asn Glu Thr                 405 410 415 Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu             420 425 430 Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro Leu Gly Val Ala Pro Thr         435 440 445 Lys Ala Lys Arg Arg Val Val Gln Arg Glu Arg Arg     450 455 460 <210> 43 <211> 1625 <212> DNA <213> Human immunodeficiency virus type 1 <400> 43 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagagt tatcaaaact 60 tgtggaaatg gggcacattg ctccttggga tattgatgat tagtagtgct acagaacaat 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga agcaaccacc actctatttt 180 gtgcatcaga tgctaaagcc tataatacag aggttcataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaat ccacaagaag taatgttaaa tgtgacagag aattttaaca 300 tgtggaaaaa tgacatggta gaacagatgc aggaggatat aatcagttta tgggatcaaa 360 gcctaaagcc atgtgtaaaa ttaaccccac tctgtgttac tttaagctac actgatgcaa 420 atagtactga tgttaatcat accaaaaata gtagtgaggg aatgatggag ggagaaaaaa 480 tgaaaaactg ctctttcaat atcaccacaa gcatgggaaa taagatgcag aaagaatatg 540 cactttttca tagacttgat gtaataccaa tggataatga aagtgctagt gctaactatt 600 ctaactatag gttaataagc tgtaacacct cagtcactac acaggcttgt ccaaaaatat 660 catttgagcc aattcccata cattattgta ccccggctgg ttttgcgatt ctaaaatgta 720 atgataagaa attcagtgga aaaggaggat gtagaaatgt cagtacagta caatgcacac 780 atggaattaa gccagtagta tcgactcaac tactgttaaa tggcagtcta gcagaagaag 840 atgtggtaat taaatctgcc aatttctcgg acaatgctaa aaccataata gtacagctga 900 atgaatctgt aataattaat tgtacaagac ccaacaacaa tacaagaaag ggtatacata 960 tgggaccagg gaaaacattt tatgcaacag gagccataat aggagatata agacaagcac 1020 attgcaatgt tagtagaaca gaccggaata acactttaaa aagggtagct aaaaaactac 1080 aagaacaatt taatacaaca aaagttgtct ttaaacaatc ctcaggaggg gacccagaaa 1140 ttgtaatgca cagttttaat tgtggagggg aatttttcta ctgtaataca tcagggctgt 1200 ttaatagtac ttggccttgg aatgatacta aagaggcaaa taacactaac acaatcacac 1260 tcccatgcaa aataaaacaa atcataaaca tgtggcaggc agtagggaaa gcaatgtatg 1320 cccctcccat tagtgggata attaaatgtg aatctaatat tacagggctg ctactaacaa 1380 gagatggtgg tagtaagaac acaacagata gtaatgacac aaacataaca caagaggtct 1440 tcagaccagg aggaggagat atgagggaca attggagaag tgaattatat aaatataaag 1500 tagtaagaat tgaaccatta ggagtagcac ccactaaggc aaaaagaaga gtggtgcaga 1560 gagaaaaaag agcagtggga ataggagctg tgttccttgg gttcttggga gcagcaggaa 1620 gcact 1625 <210> 44 <211> 489 <212> PRT <213> Human immunodeficiency virus type 1 <400> 44 Ser Ala Thr Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asn Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Met Leu Asn Val Thr Glu Asn Phe     50 55 60 Asn Met Trp Lys Asn Asp Met Val Glu Gln Met Gln Glu Asp Ile Ile 65 70 75 80 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu                 85 90 95 Cys Val Thr Leu Ser Tyr Thr Asp Ala Asn Ser Thr Asp Val Asn His             100 105 110 Thr Lys Asn Ser Ser Glu Gly Met Met Glu Gly Glu Lys Met Lys Asn         115 120 125 Cys Ser Phe Asn Ile Thr Thr Ser Met Gly Asn Lys Met Gln Lys Glu     130 135 140 Tyr Ala Leu Phe His Arg Leu Asp Val Ile Pro Met Asp Asn Glu Ser 145 150 155 160 Ala Ser Ala Asn Tyr Ser Asn Tyr Arg Leu Ile Ser Cys Asn Thr Ser                 165 170 175 Val Thr Thr Gln Ala Cys Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile             180 185 190 His Tyr Cys Thr Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys         195 200 205 Lys Phe Ser Gly Lys Gly Gly Cys Arg Asn Val Ser Thr Val Gln Cys     210 215 220 Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly 225 230 235 240 Ser Leu Ala Glu Glu Asp Val Val Ile Lys Ser Ala Asn Phe Ser Asp                 245 250 255 Asn Ala Lys Thr Ile Ile Val Gln Leu Asn Glu Ser Val Ile Ile Asn             260 265 270 Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Gly Ile His Met Gly Pro         275 280 285 Gly Lys Thr Phe Tyr Ala Thr Gly Ala Ile Ile Gly Asp Ile Arg Gln     290 295 300 Ala His Cys Asn Val Ser Arg Thr Asp Arg Asn Asn Thr Leu Lys Arg 305 310 315 320 Val Ala Lys Lys Leu Gln Glu Gln Phe Asn Thr Thr Lys Val Val Phe                 325 330 335 Lys Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Asn             340 345 350 Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gly Leu Phe Asn Ser         355 360 365 Thr Trp Pro Trp Asn Asp Thr Lys Glu Ala Asn Asn Thr Asn Thr Ile     370 375 380 Thr Leu Pro Cys Lys Ile Lys Gln Ile Ile Asn Met Trp Gln Ala Val 385 390 395 400 Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly Ile Ile Lys Cys Glu                 405 410 415 Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Ser Lys Asn             420 425 430 Thr Thr Asp Ser Asn Asp Thr Asn Ile Thr Gln Glu Val Phe Arg Pro         435 440 445 Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr     450 455 460 Lys Val Val Arg Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys 465 470 475 480 Arg Arg Val Val Gln Arg Glu Lys Arg                 485 <210> 45 <211> 1606 <212> DNA <213> Human immunodeficiency virus type 1 <400> 45 agaaagagca gaagacagtg gcaatgagag cgaaggagat caagaggaat tgtcagcact 60 cgtggagatg gggcatcatg ctccttggga tgttaatgat ctatagtact gcagaaaaaa 120 cgtgggtcac agtatattat ggggtacctg tgtggaagga agcaaacacc actctatttt 180 gtgcatcaga tgctaaagca tatgatacag aggcacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaaa taaagttgga aaatgtgaca gagaacttta 300 acatgtggaa aaacaacatg gtagaacaga tgcatgagga tattatcagt ttatgggatc 360 aaagcctaca gccaagtgta aaattaaccc cactttgtgt tactttaaat tgctctactg 420 cgaattttac taaaaggaat tttactaata gcactgagca tgaaaagccg agtgcagaaa 480 tgagaaactg ctctttcaat atcaccacaa tcgtaagaga taaggtaaca aaagaacatg 540 cactttttta tagagatgat gtagtaccaa tagataatgc tagtaataat accagttata 600 ggttaataaa ttgtaatacc tcagtcatta cacaggcctg tccaaagata tcctttgagc 660 caattcctat acattattgt gccccggctg gttttgcgat tctaaagtgt aatgataaga 720 catttaatgg aacagggcta tgtaaaaatg tcagcacagt acaatgtaca catggaatta 780 gaccagtagt gtcaactcaa ctgttgttaa atggcagtct agcagaaaaa aaggtagtag 840 ttagatctga ggagttttca gacaatgcta aatccataat agtacagctg aatacatctg 900 tagtaattaa ttgtacaaga cccggcaata atacaagaag aagcatacct atgggaccag 960 gaagagtatt ttatgcaaca gatataatag gagacataag acaggcacat tgtaacctta 1020 gtagagcagc atggaataac actttaaagc tgatagccgc agaattaaaa gaaatatata 1080 ataaaacaat agcctttaat cgatcctcag gaggggaccc agaaattgta atgcacactt 1140 ttaattgtgg gggggaattt ttctactgta atacaacaca actgtttaat agtgcttgga 1200 acagtactaa tatttatact gggaataatt ctactaatga caccatctct aatgacgcca 1260 tctcactccc atgtagaata aaacaaattg taaacatgtg gcaggaagta ggaaaagcaa 1320 tgtatgcccc tcccatcaga ggaaacatca gctgttcctc aaatattaca gggctgatat 1380 tgacaagaga tggcgggaat agtagtagta ataccgagat cttcagacct cagggaggga 1440 atataaagga caattggaga agtgaattat ataaatataa agtagtaaga attgaaccat 1500 taggattagc acccaccaag gcaaagagga gagtggtgcg gagagaaaaa gagcggtaac 1560 gttcggagct ttgttccttg ggttcttggg agcagcagga agcact 1606 <210> 46 <211> 483 <212> PRT <213> Human immunodeficiency virus type 1 <400> 46 Ser Thr Ala Glu Lys Thr Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Ile Lys Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Gln Pro Ser Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Ser Thr Ala Asn Phe Thr Lys Arg Asn             100 105 110 Phe Thr Asn Ser Thr Glu His Glu Lys Pro Ser Ala Glu Met Arg Asn         115 120 125 Cys Ser Phe Asn Ile Thr Thr Ile Val Arg Asp Lys Val Thr Lys Glu     130 135 140 His Ala Leu Phe Tyr Arg Asp Asp Val Val Pro Ile Asp Asn Ala Ser 145 150 155 160 Asn Asn Thr Ser Tyr Arg Leu Ile Asn Cys Asn Thr Ser Val Ile Thr                 165 170 175 Gln Ala Cys Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile His Tyr Cys             180 185 190 Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Thr Phe Asn         195 200 205 Gly Thr Gly Leu Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly     210 215 220 Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala 225 230 235 240 Glu Lys Lys Val Val Val Arg Ser Glu Glu Phe Ser Asp Asn Ala Lys                 245 250 255 Ser Ile Ile Val Gln Leu Asn Thr Ser Val Val Ile Asn Cys Thr Arg             260 265 270 Pro Gly Asn Asn Thr Arg Arg Ser Ile Pro Met Gly Pro Gly Arg Val         275 280 285 Phe Tyr Ala Thr Asp Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn     290 295 300 Leu Ser Arg Ala Ala Trp Asn Asn Thr Leu Lys Leu Ile Ala Ala Glu 305 310 315 320 Leu Lys Glu Ile Tyr Asn Lys Thr Ile Ala Phe Asn Arg Ser Ser Gly                 325 330 335 Gly Asp Pro Glu Ile Val Met His Thr Phe Asn Cys Gly Gly Glu Phe             340 345 350 Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn Ser Ala Trp Asn Ser Thr         355 360 365 Asn Ile Tyr Thr Gly Asn Asn Ser Thr Asn Asp Thr Ile Ser Asn Asp     370 375 380 Ala Ile Ser Leu Pro Cys Arg Ile Lys Gln Ile Val Asn Met Trp Gln 385 390 395 400 Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Asn Ile Ser                 405 410 415 Cys Ser Ser Asn Ile Thr Gly Leu Ile Leu Thr Arg Asp Gly Gly Asn             420 425 430 Ser Ser Ser Asn Thr Glu Ile Phe Arg Pro Gln Gly Gly Asn Ile Lys         435 440 445 Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu     450 455 460 Pro Leu Gly Leu Ala Pro Thr Lys Ala Lys Arg Arg Val Val Arg Arg 465 470 475 480 Glu Lys Glu              <210> 47 <211> 1613 <212> DNA <213> Human immunodeficiency virus type 1 <400> 47 agaaagagca gaagacagtg gcaatgaaag tgaaggggat caggaagaat tatcagtgct 60 tgtggggatg gggcaccatg ctcctcggga tattgatgat ctgtagtgct gcagaaaatt 120 tgtgggtcac agtctactat ggggtacctg tgtggaaaga agcaaccacc actctatttc 180 gtgcatcaga tgctaaagca tatgatacag aggtacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaag tagtattgga aaatgttaca gaaaatttta 300 atatgtggaa aaatgacatg gtagaacaga tgcaggagga tatagtcagt ttatgggatc 360 aaagcctaaa gccatgtgta gaatcaactc cactctgtgt tactctaaat tgtactgatg 420 tgaagaagaa tgctaataat accactggta ataccactga tggtaacgtg gaaaggttgg 480 agaaagaaga aataaaaaac tgctctttca atatcaccac aagcataaga gataagatgc 540 ggaaagaata tgcacttttt tatagccttg atgtagtacc aatagataag gataatacaa 600 gctataggtt gataagttgt aacacctcag tcattacaca ggcctgtcca aaagtatcct 660 ttgagccaat tcccatacat tattgtgccc cggctggttt tgcgcttcta aaatgtaatg 720 ataaggagtt caatggaaca ggaccatgta ggaatgtcag cacagtccaa tgtacacatg 780 gaattaggcc agtagtatca actcaactgc tgttaaatgg cagtctagca gaagaaaaga 840 tagtaattag atctgagaat ttcacgagca atgctaaaac tataatagta cagctgaata 900 aatctataga aattaattgt ataagaccca acaacaacac aagaagaagt atacatatag 960 gaccaggggg agcattttat gcaacagaaa taataggaga tataagacaa gcacattgta 1020 ccctcaatag aacagaatgg aataacactc taggacagat agttaaaaaa ttaagagaac 1080 aatatgggaa taaaacaata aaatttacgc agccctcctc aggaggggac ccagaagttg 1140 taatgcacag ttttaattgt ggaggggaat ttttctactg taattcatca cagctgttta 1200 atagtacttg ggatgttact gaagggtcaa ataacactga aggaagcaac gatacaggaa 1260 tcatactccc gtgcagaata aaacaaataa taaacatgtg gcagaaagta ggaaaagcaa 1320 tgtatgcccc tcccatcaga ggacaaatta actgtacatc aaatattaca gggctactat 1380 taataagaga tggtggtaac aacgggaccg acaacgggac cgagaccttc agacctggag 1440 gaggagatat gagggacaat tggagaagtg aattatataa atataaagta gtaaaaattg 1500 aaccattagg agtagcaccc accaaggcaa agagaagagt ggtgcagaga gaaaaaagag 1560 cagtgggaat aggagctttg ttccttgggt tcttgggagc agcaggaagc act 1613 <210> 48 <211> 485 <212> PRT <213> Human immunodeficiency virus type 1 <400> 48 Ser Ala Ala Glu Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Arg Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asp Met Val Glu Gln Met Gln Glu Asp Ile 65 70 75 80 Val Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Glu Ser Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Val Lys Lys Asn Ala Asn Asn             100 105 110 Thr Thr Gly Asn Thr Thr Asp Gly Asn Val Glu Arg Leu Glu Lys Glu         115 120 125 Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Ser Ile Arg Asp Lys     130 135 140 Met Arg Lys Glu Tyr Ala Leu Phe Tyr Ser Leu Asp Val Val Pro Ile 145 150 155 160 Asp Lys Asp Asn Thr Ser Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val                 165 170 175 Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His             180 185 190 Tyr Cys Ala Pro Ala Gly Phe Ala Leu Leu Lys Cys Asn Asp Lys Glu         195 200 205 Phe Asn Gly Thr Gly Pro Cys Arg Asn Val Ser Thr Val Gln Cys Thr     210 215 220 His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser 225 230 235 240 Leu Ala Glu Glu Lys Ile Val Ile Arg Ser Glu Asn Phe Thr Ser Asn                 245 250 255 Ala Lys Thr Ile Ile Val Gln Leu Asn Lys Ser Ile Glu Ile Asn Cys             260 265 270 Ile Arg Pro Asn Asn Asn Thr Arg Arg Ser Ile His Ile Gly Pro Gly         275 280 285 Gly Ala Phe Tyr Ala Thr Glu Ile Gly Asp Ile Arg Gln Ala His     290 295 300 Cys Thr Leu Asn Arg Thr Glu Trp Asn Asn Thr Leu Gly Gln Ile Val 305 310 315 320 Lys Lys Leu Arg Glu Gln Tyr Gly Asn Lys Thr Ile Lys Phe Thr Gln                 325 330 335 Pro Ser Ser Gly Gly Asp Pro Glu Val Val Met His Ser Phe Asn Cys             340 345 350 Gly Gly Glu Phe Phe Tyr Cys Asn Ser Ser Gln Leu Phe Asn Ser Thr         355 360 365 Trp Asp Val Thr Glu Gly Ser Asn Asn Thr Glu Gly Ser Asn Asp Thr     370 375 380 Gly Ile Ile Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln 385 390 395 400 Lys Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Gln Ile Asn                 405 410 415 Cys Thr Ser Asn Ile Thr Gly Leu Leu Leu Ile Arg Asp Gly Gly Asn             420 425 430 Asn Gly Thr Asp Asn Gly Thr Glu Thr Phe Arg Pro Gly Gly Gly Asp         435 440 445 Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys     450 455 460 Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val 465 470 475 480 Gln Arg Glu Lys Arg                 485 <210> 49 <211> 1616 <212> DNA <213> Human immunodeficiency virus type 1 <400> 49 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaggaat tatcagtgct 60 tgtggacatg gggcacgatg ctccttggga tgttgatgat ctgtagtgct gtagaacaat 120 tgtgggtcac agtctattat ggggtgcctg tgtgggaaga agcgaccacc actctatttt 180 gtgcatcaga tgctaaaaca tatgatccag aggtacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaag tagtattggg aaatgtgaca gaaaacttta 300 acatgtggaa aaatgacatg gtaaaccaaa tgcatgagga tataatcagt ttatgggatc 360 aaagtttaaa gccatgtgca aaattaaccc cactctgtgt tactctaaat tgcactgata 420 agttgaatat taatactacc agtaccaata gtagtaccaa taatactact agtagtggag 480 tggatgaagg gggaatgaaa aactgctctt tcaatgtcac cacaagcata agagataggg 540 tgcagaaaga atatgcactt ttttataaac ctgatgtagt accaatagat gataatacta 600 ataatactag ctataggttg ataaattgta acacctcagt cattacacaa gcctgtccaa 660 aggtaacctt tgatccaatt cccatacatt attgtgcccc ggctggtttt gcgattctaa 720 aatgtaacaa taagacgttc aatggatcag gaccatgtac aaatgtcagc acagtacaat 780 gtacacatgg aattaaacca gtggtgtcga ctcaattgct gttaaatggc agtctagcag 840 aggaagaaat agtaatcagg tctgaagatt tcacggacaa tgatagaacc ataatagtac 900 agctgaatga atctgtagta attcattgta caagacccaa caacaataca agaaaaagta 960 tacacctagg accagggagt gcattttatg caacaggaga tataatagga gatataaaac 1020 aagcacattg taacattagt agagcaaatt ggactaacac cttaaaacag atagctggaa 1080 aattaaaaga acagtttgga aataagacaa tattctttaa tcaatcctca ggaggggatc 1140 cagaaattgt aacacacagt ttcaattgta gaggggaatt tttctactgt aatacatcac 1200 aattgtttaa cagtacttgg cttcataata atagtactgg gaatgatact gaaaagaatg 1260 gtaatatcac actcccacgc agaataaaac aaattataaa catgtggcag caagtaggaa 1320 aagcaatgta tgccccccct gtcaaaggac taattacatg ttcatcaaat attacaggac 1380 tgctattagt aagagatggt ggtaacaaca ccaacgccac cgacaccgag accttcagac 1440 ctggaggagg agatatgagg gacaattgga gaagtgaatt atataaatat aaagtagtaa 1500 aaatcaaacc attaggaata gcacccacca aggcaaaaag aagagtggtg cagagagaaa 1560 aaagagcagc actaggagct atgttccttg ggttcttggg agcagcagga agcact 1616 <210> 50 <211> 487 <212> PRT <213> Human immunodeficiency virus type 1 <400> 50 Ser Ala Val Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Glu Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Thr             20 25 30 Tyr Asp Pro Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Gly Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asp Met Val Asn Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Ala Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Lys Leu Asn Ile Asn Thr Thr             100 105 110 Ser Thr Asn Ser Ser Thr Asn Asn Thr Thr Ser Ser Gly Val Asp Glu         115 120 125 Gly Gly Met Lys Asn Cys Ser Phe Asn Val Thr Thr Ser Ile Arg Asp     130 135 140 Arg Val Gln Lys Glu Tyr Ala Leu Phe Tyr Lys Pro Asp Val Val Pro 145 150 155 160 Ile Asp Asp Asn Thr Asn Asn Thr Ser Tyr Arg Leu Ile Asn Cys Asn                 165 170 175 Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Thr Phe Asp Pro Ile             180 185 190 Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn         195 200 205 Asn Lys Thr Phe Asn Gly Ser Gly Pro Cys Thr Asn Val Ser Thr Val     210 215 220 Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu 225 230 235 240 Asn Gly Ser Leu Ala Glu Glu Glu Ile Val Ile Arg Ser Glu Asp Phe                 245 250 255 Thr Asp Asn Asp Arg Thr Ile Ile Val Gln Leu Asn Glu Ser Val Val             260 265 270 Ile His Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile His Leu         275 280 285 Gly Pro Gly Ser Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile     290 295 300 Lys Gln Ala His Cys Asn Ile Ser Arg Ala Asn Trp Thr Asn Thr Leu 305 310 315 320 Lys Gln Ile Ala Gly Lys Leu Lys Glu Gln Phe Gly Asn Lys Thr Ile                 325 330 335 Phe Phe Asn Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Thr His Ser             340 345 350 Phe Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gln Leu Phe         355 360 365 Asn Ser Thr Trp Leu His Asn Asn Ser Thr Gly Asn Asp Thr Glu Lys     370 375 380 Asn Gly Asn Ile Thr Leu Pro Arg Arg Ile Lys Gln Ile Ile Asn Met 385 390 395 400 Trp Gln Gln Val Gly Lys Ala Met Tyr Ala Pro Pro Val Lys Gly Leu                 405 410 415 Ile Thr Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Val Arg Asp Gly             420 425 430 Gly Asn Asn Thr Asn Ala Thr Asp Thr Glu Thr Phe Arg Pro Gly Gly         435 440 445 Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val     450 455 460 Val Lys Ile Lys Pro Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg 465 470 475 480 Val Val Gln Arg Glu Lys Arg                 485 <210> 51 <211> 1613 <212> DNA <213> Human immunodeficiency virus type 1 <400> 51 agaaagagca gaagacagtg gcaatgagag tgagggggac caggaagaat tatcagcact 60 tgtggagatg gggcatcatg ctccttggga tgtcaatgat ctgtaatgct acaaaagatt 120 tgtgggtcac agtttattat ggggtacctg tatggaaaga agcaaacacc agtctatttt 180 gtgcatcaga tgctaaagca tatgatacag aggtacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaag tattcatgaa caatgtgaca gaaaatttta 300 acatgtggaa aaataacatg gtagaacaaa tgcatgagga tataatcagt ttatgggatc 360 aaagcctaaa accatgtgta aaattaaccc cactcggtgt tactctagat tgcactaagg 420 ctaatattac caataatagt accactaata gtagcggggg aatagaggag ggaagagaca 480 tagaaaattg ctctttcaat atcaccacaa acataagaga taagataaag aaagaatatg 540 cactttttta tagccttgat gtgatagcaa tagatgatag tagtaatagt agtaatagaa 600 gctataggtt gagaggttgt aacacctcaa ccatcacaca ggcctgtcca aaggtaacct 660 ttgagccaat tccaatacat tattgtgccc cagctggttt tgcgattcta aagtgtaacg 720 ataagaagtt caatggaaca ggaccatgta aaaatgtcag tacagtacaa tgtacacatg 780 gaattaggcc agtagtatca actcaactgc tgctaaatgg cagtatagca gaaaaagagg 840 tagtaattag gtccgctaat ttcacggaca atgctaaaac cataatagta cagctgaata 900 actctgtaca aattaattgc acaagacccg gcaacaatac aagaaaaagt atacatatag 960 gaccaggcag agcattttat gcacatgaaa taatagggga gataagacaa gcacattgta 1020 cccttaacag aacacaatgg aataacactt taaaacagat agttataaaa ttaagagaac 1080 aatttaacaa taagacaata gtctttaatc actcctcagg aggggaccca gaaattgtaa 1140 cacacagttt taattgtgga ggggaatttt tctactgtaa tacatcacaa ttatttaata 1200 gtacctggag gagtaatgaa actgtaaatg acactatggg aaaggacaca aatgacacaa 1260 caatcacact cccatgcaga ataaaacaaa ttataaacat gtggcaggaa gtaggaaaag 1320 caatgtatgc cccgcccatc agaggacaaa ttagctgttc atcaaatatt acagggctgc 1380 tattaacaag agatggtggt gtgaacgaga ccaacgccac cgaggtcttc agacctggag 1440 gaggagatat gagggacaat tggagaagtg aattatataa atataaagta gtagaaattg 1500 aaccattagg aatagcaccc accaaggcaa agagaagagt ggtgcagaga gagaaaagag 1560 cagtgggaat aggagctgtg ttccttgggt tcttgggagc agcaggaagc act 1613 <210> 52 <211> 485 <212> PRT <213> Human immunodeficiency virus type 1 <400> 52 Asn Ala Thr Lys Asp Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Asn Thr Ser Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Phe Met Asn Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Gly Val Thr Leu Asp Cys Thr Lys Ala Asn Ile Thr Asn Asn Ser             100 105 110 Thr Thr Asn Ser Ser Gly Gly Ile Glu Glu Gly Arg Asp Ile Glu Asn         115 120 125 Cys Ser Phe Asn Ile Thr Thr Asn Ile Arg Asp Lys Ile Lys Lys Glu     130 135 140 Tyr Ala Leu Phe Tyr Ser Leu Asp Val Ile Ala Ile Asp Asp Ser Ser 145 150 155 160 Asn Ser Ser Asn Arg Ser Tyr Arg Leu Arg Gly Cys Asn Thr Ser Thr                 165 170 175 Ile Thr Gln Ala Cys Pro Lys Val Thr Phe Glu Pro Ile Pro Ile His             180 185 190 Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Lys         195 200 205 Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys Thr     210 215 220 His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser 225 230 235 240 Ile Ala Glu Lys Glu Val Val Ile Arg Ser Ala Asn Phe Thr Asp Asn                 245 250 255 Ala Lys Thr Ile Ile Val Gln Leu Asn Asn Ser Val Gln Ile Asn Cys             260 265 270 Thr Arg Pro Gly Asn Asn Thr Arg Lys Ser Ile His Ile Gly Pro Gly         275 280 285 Arg Ala Phe Tyr Ala His Glu Ile Ile Gly Glu Ile Arg Gln Ala His     290 295 300 Cys Thr Leu Asn Arg Thr Gln Trp Asn Asn Thr Leu Lys Gln Ile Val 305 310 315 320 Ile Lys Leu Arg Glu Gln Phe Asn Asn Lys Thr Ile Val Phe Asn His                 325 330 335 Ser Ser Gly Gly Asp Pro Glu Ile Val Thr His Ser Phe Asn Cys Gly             340 345 350 Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gln Leu Phe Asn Ser Thr Trp         355 360 365 Arg Ser Asn Glu Thr Val Asn Asp Thr Met Gly Lys Asp Thr Asn Asp     370 375 380 Thr Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp 385 390 395 400 Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Gln Ile                 405 410 415 Ser Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly             420 425 430 Val Asn Glu Thr Asn Ala Thr Glu Val Phe Arg Pro Gly Gly Gly Asp         435 440 445 Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Glu     450 455 460 Ile Glu Pro Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val 465 470 475 480 Gln Arg Glu Lys Arg                 485 <210> 53 <211> 1658 <212> DNA <213> Human immunodeficiency virus type 1 <400> 53 agaaagagca gaagacagtg gcaatgagag cgaaggggat caggaagaat tggcagcact 60 tgtggagatg gggcaccatg ctcccatggg gcaccatgct ccttgggatg ttaatgatga 120 tctgtagtgc tgcagaagaa aaatgggtca cagtctatta tggggtacct gtgtggaaag 180 aagcaaccac cactctattt tgtgcatcag atgctaaagc atatgacaca gaggtacata 240 atgtttgggc cacacatgcc tgtgtaccca cagaccctaa cccacaagaa gtagtattgg 300 gaaatgtgac agaaaatttt aatgtgtgga aaaatgacat ggtagaacag atgcatgaag 360 atataatcag cttatgggat caaagcctaa agccatgtgt aaaattaacc ccactctgtg 420 ttgctttaaa ttgcactaat gtgaatgata ctaggacaaa caatagtagt agtagtgata 480 aaaatgatgc taaaaccaat agtagtagta gttgggaaag gatggaagga gaagtaaaaa 540 actgctcttt caatgttacc acaagaataa gaaacaaggt gcagaaagaa tatgcacttt 600 tttataagct tgatgtagtg ccaatagaga aggataatgc aagctataca ttgataaatt 660 gtaacacctc agtcattaca caggcctgtc caaaggtatc ttttgaacca attcccatac 720 attattgtgc cccggctggt tttgcgattc taaagcgtaa tgataagaag ttcaatggaa 780 aaggcccatg tacaaatgtc agcacagtac gatgtacaca tggaattagg ccagtagtgt 840 caactcaact actgttaaat ggcagtctag cagaagaagg ggtagtaatt agatctgaaa 900 atctcacgaa caatgttaaa accataatag tacagctgaa caaatctgta aaaattaatt 960 gtacaagacc caacaacaat acaagaaaaa gtataaatat aggaccaggg agagcatttt 1020 atgcaacagg agcaataata ggaaatatga gacaagcaca ttgtaacctt aatggaacag 1080 aatggaagaa cactttaaga caggtagtta taagcttaag agagaaattt gggaagaaga 1140 caatagtctt caaccaatcc tcaggagggg atttagaaat tataatgcac aattttaatt 1200 gtggagggga atttttctac tgtgatacaa cacagctgtt taatagtact tggctgccta 1260 atgagactac agagtcaaat aacattactg gaggacctaa tgacacactc acgctcccat 1320 gtagaataaa acaaattata aacagatggc aggaagtagg aaaagcaatg tatgcccctc 1380 ccatcagtgg gcaaattaga tgctcatcaa atattacggg gctgctatta acaagagatg 1440 gtggtgagga gcagaatgac actgaggtct ttagacctgg aggaggagat atgagggaca 1500 attggagaag tgaattatat aaatataaag tagtaagaat tgagccatca ggagtagcac 1560 ccaccaaggc aaagagaaga gtggtgcaaa gagacaaaag agcagtggga gcactaggag 1620 ctatgttcct tgggttcttg ggagcagcag gaagcact 1658 <210> 54 <211> 490 <212> PRT <213> Human immunodeficiency virus type 1 <400> 54 Ser Ala Ala Glu Glu Lys Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Gly Asn Val Thr Glu Asn     50 55 60 Phe Asn Val Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Ala Leu Asn Cys Thr Asn Val Asn Asp Thr Arg Thr Asn             100 105 110 Asn Ser Ser Ser Ser Asp Lys Asn Asp Ala Lys Thr Asn Ser Ser Ser         115 120 125 Ser Trp Glu Arg Met Glu Gly Glu Val Lys Asn Cys Ser Phe Asn Val     130 135 140 Thr Thr Arg Ile Arg Asn Lys Val Gln Lys Glu Tyr Ala Leu Phe Tyr 145 150 155 160 Lys Leu Asp Val Val Pro Ile Glu Lys Asp Asn Ala Ser Tyr Thr Leu                 165 170 175 Ile Asn Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser             180 185 190 Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile         195 200 205 Leu Lys Arg Asn Asp Lys Lys Phe Asn Gly Lys Gly Pro Cys Thr Asn     210 215 220 Val Ser Thr Val Arg Cys Thr His Gly Ile Arg Pro Val Val Ser Thr 225 230 235 240 Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Gly Val Val Ile Arg                 245 250 255 Ser Glu Asn Leu Thr Asn Asn Val Lys Thr Ile Ile Val Gln Leu Asn             260 265 270 Lys Ser Val Lys Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys         275 280 285 Ser Ile Asn Ile Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly Ala Ile     290 295 300 Ile Gly Asn Met Arg Gln Ala His Cys Asn Leu Asn Gly Thr Glu Trp 305 310 315 320 Lys Asn Thr Leu Arg Gln Val Val Ile Ser Leu Arg Glu Lys Phe Gly                 325 330 335 Lys Lys Thr Ile Val Phe Asn Gln Ser Ser Gly Gly Asp Leu Glu Ile             340 345 350 Ile Met His Asn Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asp Thr         355 360 365 Thr Gln Leu Phe Asn Ser Thr Trp Leu Pro Asn Glu Thr Thr Glu Ser     370 375 380 Asn Asn Ile Thr Gly Gly Pro Asn Asp Thr Leu Thr Leu Pro Cys Arg 385 390 395 400 Ile Lys Gln Ile Ile Asn Arg Trp Gln Glu Val Gly Lys Ala Met Tyr                 405 410 415 Ala Pro Pro Ile Ser Gly Gln Ile Arg Cys Ser Ser Asn Ile Thr Gly             420 425 430 Leu Leu Leu Thr Arg Asp Gly Gly Glu Glu Gln Asn Asp Thr Glu Val         435 440 445 Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu     450 455 460 Tyr Lys Tyr Lys Val Val Arg Ile Glu Pro Ser Gly Val Ala Pro Thr 465 470 475 480 Lys Ala Lys Arg Arg Val Val Gln Arg Asp                 485 490 <210> 55 <211> 1658 <212> DNA <213> Human immunodeficiency virus type 1 <400> 55 agaaagagca gaagacagtg gcaatgaaag tgaaggggac caggaagaat tatcagcact 60 tatggagatg gggcaccatg ctcctatgga gatggggcac catgctcctt gggctattaa 120 tgatctgtaa tgctatagaa gaatcgtggg tcacagtcca ttatggagta cctgtgtgga 180 aagaagcaaa caccactctg ttttgtgcat cagatgctaa agcatatgat acagaggtac 240 ataatgtttg ggccacacat gcctgtgtac ccacaaaccc caacccacaa gaagtagact 300 tgggaaatgt gacagaaaat tttaatgcat ggaaaaatga catggtagaa caaatgcatg 360 aggatataat tagtttatgg gatcaaagcc taaagccatg tgtaaaatta actccactct 420 gtgttactct acagtgcact gatttgagga atgatactaa taccactagt agtcctaata 480 ccactagtgg taactggatg gataaaaggg aaatgaaaaa ctgctctttc aatatcacca 540 caagcataag agataagctg cagaaaacat ttgcactttt ttataaactt gatatagtac 600 caataaatga ggacaaaaac agtagtaata ttgataatac cagttatagg ttgataagtt 660 gtaatacctc agtcattaca caggcctgtc caaaggtatc ctttgagcca attcccatac 720 attattgtgc cccggctggt tttgcgattc taaaatgtaa agatgaggag ttcaatggaa 780 caggaccatg taaaaatgtc agtacagtac aatatacaca tggaattagg ccagtagtat 840 caactcaact gctgttaaat ggcagtctag cagaacaagg ggtagtactt agatctaaaa 900 atatctcaga caatactaaa accataatag tacagctaaa agaagctgta acaattaagt 960 gtacaagacc caacaacaat acaagaaaaa gtatacatat aggacctggg agagcatttt 1020 atgcaacagg agacataata ggagatataa gacaagccca ttgtaacatc agtgcaacaa 1080 agtggaatga cacgttacgt cagatagttg aaaaattaca aggatcattt aagaataaaa 1140 caataagctt caagcgatcc tcaggagggg atccagagat tgtaatgcac agttttaatt 1200 gtggagggga atttttctat tgtaattcaa caaaactgtt taatagtact tggtatagta 1260 atgggactag tacttttgat aatactactg aacgaacaaa tgacactatc atactcccat 1320 gcagaataaa acaaattata aacatgtggc aggaagtagg aaaagcaatg tatgcccctc 1380 ccatcccagg actaattaac tgttcatcaa atattacagg actgctatta ataagagatg 1440 gtggtaataa ctatactgac aatactgaga tcttcagacc tggaggagga gacatgaggg 1500 acaattggag aagtgaatta tataaatata aagtagtaaa agttgaacca ttaggtatag 1560 cacccaccaa ggcaaagaga agagtggtac agagagaaaa aagagcagtg ggaataggag 1620 cgtttttcct tgggttcttg ggagcagcag gaagcact 1658 <210> 56 <211> 490 <212> PRT <213> Human immunodeficiency virus type 1 <400> 56 Asn Ala Ile Glu Glu Ser Trp Val Thr Val His Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asn Pro Asn Pro Gln Glu Val Asp Leu Gly Asn Val Thr Glu Asn     50 55 60 Phe Asn Ala Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Gln Cys Thr Asp Leu Arg Asn Asp Thr Asn Thr             100 105 110 Thr Ser Ser Pro Asn Thr Thr Ser Gly Asn Trp Met Asp Lys Arg Glu         115 120 125 Met Lys Asn Cys Ser Phe Asn Ile Thr Thr Ser Ile Arg Asp Lys Leu     130 135 140 Gln Lys Thr Phe Ala Leu Phe Tyr Lys Leu Asp Ile Val Pro Ile Asn 145 150 155 160 Glu Asp Lys Asn Ser Ser Asn Ile Asp Asn Thr Ser Tyr Arg Leu Ile                 165 170 175 Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe             180 185 190 Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu         195 200 205 Lys Cys Lys Asp Glu Glu Phe Asn Gly Thr Gly Pro Cys Lys Asn Val     210 215 220 Ser Thr Val Gln Tyr Thr His Gly Ile Arg Pro Val Val Ser Thr Gln 225 230 235 240 Leu Leu Leu Asn Gly Ser Leu Ala Glu Gln Gly Val Val Leu Arg Ser                 245 250 255 Lys Asn Ile Ser Asp Asn Thr Lys Thr Ile Ile Val Gln Leu Lys Glu             260 265 270 Ala Val Thr Ile Lys Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser         275 280 285 Ile His Ile Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly Asp Ile Ile     290 295 300 Gly Asp Ile Arg Gln Ala His Cys Asn Ile Ser Ala Thr Lys Trp Asn 305 310 315 320 Asp Thr Leu Arg Gln Ile Val Glu Lys Leu Gln Gly Ser Phe Lys Asn                 325 330 335 Lys Thr Ile Ser Phe Lys Arg Ser Ser Gly Gly Asp Pro Glu Ile Val             340 345 350 Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr         355 360 365 Lys Leu Phe Asn Ser Thr Trp Tyr Ser Asn Gly Thr Ser Thr Phe Asp     370 375 380 Asn Thr Thr Glu Arg Thr Asn Asp Thr Ile Ile Leu Pro Cys Arg Ile 385 390 395 400 Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala                 405 410 415 Pro Pro Ile Pro Gly Leu Ile Asn Cys Ser Ser Asn Ile Thr Gly Leu             420 425 430 Leu Leu Ile Arg Asp Gly Gly Asn Asn Tyr Thr Asp Asn Thr Glu Ile         435 440 445 Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu     450 455 460 Tyr Lys Tyr Lys Val Val Lys Val Glu Pro Leu Gly Ile Ala Pro Thr 465 470 475 480 Lys Ala Lys Arg Arg Val Val Gln Arg Glu                 485 490 <210> 57 <211> 1655 <212> DNA <213> Human immunodeficiency virus type 1 <400> 57 agaaagagca gaagacagtg gcaatgagag tgaaggagat caggaagaat tgtcagcgct 60 tgtggacatg gggcaccatg ctccttggga tgttgatgat ctgtagtact gcagaacaac 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga agcaactacc actttatttt 180 gtgcatcaga tgctaaagca tatgacacag aagcacataa tgtttgggcc acacatgcct 240 gtgtacccac ggaccctaac ccacaagaag tagtaataaa tgtgacagaa aattttaaca 300 tgtggaaaaa tgacatggta gaacagatgc atgaggacat aatcagtgta tgggaccaga 360 gtctaaagcc atgtgtaaaa ttaaccccac tctgtgttac tttaaattgc actaattgga 420 atggtactaa taccaataat gctaatacta ccagtagtcc taatattacc agtactacta 480 ctgccaatat ttatgagaaa agaatggaag aaggagaaat acaaaactgc actttcaatg 540 tcaccacaag cataagggat aaggtaaaag aagaatatgc acttttttat agatctgatg 600 taggccaaat aggtaataat agtaataata catatacatt gataaattgt aattcctcag 660 tcattacaca ggctcgtcca aagatatcct ttgaaccaat tcccatacat tattgtaccc 720 cggctggttt tgcgattcta aaatgcaata ataagacctt caatggaaca ggaccatgta 780 acaatgtcag cacagtacag tgtacacatg gtattaggcc agtagtatca actcaattgt 840 tgttaaatgg cagtctagca gaagatgaga taatgattag atctgcaaat ctctcggaca 900 atactaaaaa cataatagta cagctgaata aatctgtaga aattaattgt acaagaccca 960 acaataatac aagaaaaagt ataaatatag gaccagggag agcattttat gcaacaggag 1020 atataatagg aaacataaga catgcatatt gtaccattaa tgaaacaaaa tggaatgaaa 1080 ctttaagaca gatagctaca aaattacaca aacaatttaa taaaacaata atctttgagc 1140 agtcctcagg aggagaccca gaaattacaa cgcacagttt taattgtgga ggggaatttt 1200 tctactgtaa tacaacaccg ctgtttaata gcacttgggt taagactcag aatgatacta 1260 tagggtctaa gactcagaat gctactacag ggttaaatgg cactatcata ctcccatgca 1320 gaataaaaca aatcataaac agatggcagg aagtaggaag agcaatgtat gcccctccca 1380 tcaaaggaat aattagatgt tcatcaaata ttacagggct gatattgaca agagatggtg 1440 gtggtaatga gagcagggaa aatgagacct tcagacctgg aggaggagat atgagggaca 1500 attggagaag tgaattatat aaatataaag tagtaaaaat tgagccaata ggactggcac 1560 ccaccaaggc aaagagaaga gtggtgcaga gagaaaaaag agcggtaacg ctgggagcta 1620 tgttccctgg gttcttggga gcagcaggaa gcact 1655 <210> 58 <211> 499 <212> PRT <213> Human immunodeficiency virus type 1 <400> 58 Ser Thr Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Ile Asn Val Thr Glu Asn Phe     50 55 60 Asn Met Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile Ile 65 70 75 80 Ser Val Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu                 85 90 95 Cys Val Thr Leu Asn Cys Thr Asn Trp Asn Gly Thr Asn Thr Asn Asn             100 105 110 Ala Asn Thr Thr Ser Ser Pro Asn Ile Thr Ser Thr Thr Thr Ala Asn         115 120 125 Ile Tyr Glu Lys Arg Met Glu Glu Gly Glu Ile Gln Asn Cys Thr Phe     130 135 140 Asn Val Thr Thr Ser Ile Arg Asp Lys Val Lys Glu Glu Tyr Ala Leu 145 150 155 160 Phe Tyr Arg Ser Asp Val Gly Gln Ile Gly Asn Asn Ser Asn Asn Thr                 165 170 175 Tyr Thr Leu Ile Asn Cys Asn Ser Ser Val Ile Thr Gln Ala Arg Pro             180 185 190 Lys Ile Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Thr Pro Ala Gly         195 200 205 Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro     210 215 220 Cys Asn Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val 225 230 235 240 Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Asp Glu Ile                 245 250 255 Met Ile Arg Ser Ala Asn Leu Ser Asp Asn Thr Lys Asn Ile Ile Val             260 265 270 Gln Leu Asn Lys Ser Val Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn         275 280 285 Thr Arg Lys Ser Ile Asn Ile Gly Pro Gly Arg Ala Phe Tyr Ala Thr     290 295 300 Gly Asp Ile Ile Gly Asn Ile Arg His Ala Tyr Cys Thr Ile Asn Glu 305 310 315 320 Thr Lys Trp Asn Glu Thr Leu Arg Gln Ile Ala Thr Lys Leu His Lys                 325 330 335 Gln Phe Asn Lys Thr Ile Ile Phe Glu Gln Ser Ser Gly Gly Asp Pro             340 345 350 Glu Ile Thr Thr His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys         355 360 365 Asn Thr Thr Pro Leu Phe Asn Ser Thr Trp Val Lys Thr Gln Asn Asp     370 375 380 Thr Ile Gly Ser Lys Thr Gln Asn Ala Thr Thr Gly Leu Asn Gly Thr 385 390 395 400 Ile Ile Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Arg Trp Gln Glu                 405 410 415 Val Gly Arg Ala Met Tyr Ala Pro Pro Ile Lys Gly Ile Ile Arg Cys             420 425 430 Ser Ser Asn Ile Thr Gly Leu Ile Leu Thr Arg Asp Gly Gly Gly Asn         435 440 445 Glu Ser Arg Glu Asn Glu Thr Phe Arg Pro Gly Gly Gly Asp Met Arg     450 455 460 Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu 465 470 475 480 Pro Ile Gly Leu Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg                 485 490 495 Glu lys arg              <210> 59 <211> 1637 <212> DNA <213> Human immunodeficiency virus type 1 <400> 59 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tatcagcact 60 tgtggacatg gagcaacatg ctcacgatgc tccttgggat gttaatgatc tgtagtgctg 120 cagatcaatt gtgggtcaca gtctattatg gggtacctgt gtggaaagaa acaaccacca 180 ctctattttg tgcatcagat gctaaagcat atgataaaga ggtacataat gtttgggcca 240 cacatgcctg tgtacccaca gaccccaacc cacaagaagt aatattggaa aatgtgacag 300 aaaattttaa cgcgtggaaa aatgacatgg tagaacagat gcatgaggat ataattagtt 360 tatgggatca aagcttaaag ccatgtgtaa aattaacccc actctgtgtt actttaaatt 420 gcactgatgc taatattact aataccaatg ataatgagcc caatagtagt gtggtgaaac 480 tgatagagaa aggagaaata aaaaactgct ctttcaatat caccacaagc ataagagata 540 agatgcagaa agcatatgca cttttttata aacttgatgt agaaccaata gagaataata 600 ctactagcta taggttgata agttgtaaca cctcagtcat tacacaagcc tgtccaaagg 660 tatcctttga gccaattccc atacattttt gtgccccggc tggttttgcg attctaaagt 720 gtaacaataa gacattcgag ggaaaaggac catgtaaaaa tatcagcaca gtacaatgta 780 cacatggaat taggccagta gtatcaactc aattgctgtt aaatggcagt ctggcagaag 840 aagagatagt gattagatct gacaattttt caaacagtgc taaaaccata atagtacagt 900 tgaatgcatc tgtagaaatt aatcgtacaa gacccaacaa caatacgaga aaaggtatag 960 ttataggacc agggagaaaa gttattgcaa cagaaaaaat aataggagat gtaagacaag 1020 cacattgtaa cattagtata acaaaatgga ataatacttt aggccatata gttaataaat 1080 taagaaaaca atttggggaa aataaaacaa tagtctttaa gcaacactca ggaggggatc 1140 cagaagttat aatgcataat tttaattgtg caggggaatt tttctactgt aatacaacag 1200 gactgtttaa tagcacttgg cattggaatg gtacttggag tggtactgaa aggagaaata 1260 gcactgaagg aaatgacaca cttacactcc catgcagaat aaaacaaatt ataaacatgt 1320 ggcaggaagt aggaaaagca atgtatgccc ctcccgttaa cggacagatt agatgtttat 1380 caaatattac aggactgcta ttaacaagag atggtggtaa taacaataac acaaacgaca 1440 ccgaaacctt cagacctgaa ggaggagata tgagggacaa ttggagaagt gaattatata 1500 aatataaagt agtaagaatt gaaccattag gagtagcacc caccaaggca aagagaagag 1560 tggtgcagag agaaaaaaga gcactgggag taggagcagc tttgttcctt gggttcttgg 1620 gagcagcagg aagcact 1637 <210> 60 <211> 489 <212> PRT <213> Human immunodeficiency virus type 1 <400> 60 Ser Ala Ala Asp Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Thr Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Lys Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Ile Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Ala Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Ala Asn Ile Thr Asn Thr Asn             100 105 110 Asp Asn Glu Pro Asn Ser Ser Val Val Lys Leu Ile Glu Lys Gly Glu         115 120 125 Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Ser Ile Arg Asp Lys Met     130 135 140 Gln Lys Ala Tyr Ala Leu Phe Tyr Lys Leu Asp Val Glu Pro Ile Glu 145 150 155 160 Asn Asn Thr Thr Ser Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val Ile                 165 170 175 Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Phe             180 185 190 Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe         195 200 205 Glu Gly Lys Gly Pro Cys Lys Asn Ile Ser Thr Val Gln Cys Thr His     210 215 220 Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu 225 230 235 240 Ala Glu Glu Glu Ile Val Ile Arg Ser Asp Asn Phe Ser Asn Ser Ala                 245 250 255 Lys Thr Ile Ile Val Gln Leu Asn Ala Ser Val Glu Ile Asn Arg Thr             260 265 270 Arg Pro Asn Asn Asn Thr Arg Lys Gly Ile Val Ile Gly Pro Gly Arg         275 280 285 Lys Val Ile Ala Thr Glu Lys Ile Ile Gly Asp Val Arg Gln Ala His     290 295 300 Cys Asn Ile Ser Ile Thr Lys Trp Asn Asn Thr Leu Gly His Ile Val 305 310 315 320 Asn Lys Leu Arg Lys Gln Phe Gly Glu Asn Lys Thr Ile Val Phe Lys                 325 330 335 Gln His Ser Gly Gly Asp Pro Glu Val Ile Met His Asn Phe Asn Cys             340 345 350 Ala Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gly Leu Phe Asn Ser Thr         355 360 365 Trp His Trp Asn Gly Thr Trp Ser Gly Thr Glu Arg Arg Asn Ser Thr     370 375 380 Glu Gly Asn Asp Thr Leu Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile 385 390 395 400 Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Val Asn                 405 410 415 Gly Gln Ile Arg Cys Leu Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg             420 425 430 Asp Gly Gly Asn Asn Asn Asn Thr Asn Asp Thr Glu Thr Phe Arg Pro         435 440 445 Glu Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr     450 455 460 Lys Val Val Arg Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys 465 470 475 480 Arg Arg Val Val Gln Arg Glu Lys Arg                 485 <210> 61 <211> 1678 <212> DNA <213> Human immunodeficiency virus type 1 <400> 61 agaaagagca gaagacagtg gaatgagagt gaaggggatc aggaagaatt atcagcactt 60 gtggatatgg ggcatcttgc tccctgggat gttgatgatc tgtagtgctg cagacaagtt 120 gtgggtcaca gtctattatg gggtacctgt gtggaaagaa gcaaccacca ctctattttg 180 tgcatcagat gctaaagcat atagtgcaga ggtacataat gtctgggcca cacatgcctg 240 tgtacccaca gaccccgacc cacaggaaat agtattggaa aatgtaacag aaaattttaa 300 catgtggaaa aataacatgg tagaacagat gcaggaggat ataatcagtt tatgggatca 360 aagcctaaag ccatgtgtaa aattaacccc tctctgtgtc actttaaacc gcactgatga 420 attgcggact actaataaga ctactaataa gaccaatgat acagagacga atactactaa 480 taccaccagc tgggaaaaag gggaaatgaa aaactgctct tttgatgtca ccacaaacat 540 aagagataag tggcagagag aatatgcact tttttataag cttgatgtag taccaataga 600 taatgatggt aatggtaata gtagtaataa tgccactgat aataataata ctaccaaata 660 taccaactat aggttgataa gttgtaacac ctcagttatt acacaggcct gtccaaaggt 720 atcctttgag ccaattccca tacattattg tgccccagct ggttttgcga ttctaaagtg 780 taaagatgag aagttcagtg gaacaggacc atgtaaaaat gtcagcacag tacaatgcac 840 acatggaatt aggccagtag tatcaactca actgctgttg aatggcagtc tagcaaaaga 900 agagataata attagatctg aaaatctcac gaacaatgct aaaaccataa tagtacagct 960 gaatgaatct gtatcaatta attgtataag acccaacaat aatacaagaa gaggtatacc 1020 tataggacca gggcaagcat tttatgcaac aggggatata ataggggata taagaaaagc 1080 acattgtata gttaacagta cacaatggaa taacacttta gcacaggtag ccataaaatt 1140 aaatgaacac tttccaaata aaacaatagt ctttaagcag tcctcaggag gggacccaga 1200 aattgtaatg cacagtttta attgtggagg ggaatttttc tactgtgatt caacaccact 1260 gtttaacaat acttggaatg aaacacattt taataatact tgggatagta ttgaaaaggg 1320 aaaaatcata ctccaatgca gaataaaaca aattataaat atgtggcagg aagtaggaaa 1380 agcaatgtat gcccctccca tcagagggct gattaactgt acatcaaaca ttacagggct 1440 actattaaca agagatggtg gcaagaaaga gaatgagagt gatactatcg agatcttcag 1500 acctggagga ggagacatga ggaacaattg gagaagtgaa ttatataaat ataaagtagt 1560 aaaaattgaa ccattaggag tagcacccac caaggcaaaa agaagagtgg tgcagagaga 1620 aaaaagagca gcgctaggag ctttgttcct tgggttcttg ggagcagcag gaagcact 1678 <210> 62 <211> 508 <212> PRT <213> Human immunodeficiency virus type 1 <400> 62 Ser Ala Ala Asp Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Ser Ala Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asp Pro Gln Glu Ile Val Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met Gln Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Arg Thr Asp Glu Leu Arg Thr Thr Asn Lys             100 105 110 Thr Thr Asn Lys Thr Asn Asp Thr Glu Thr Asn Thr Thr Asn Thr Thr         115 120 125 Ser Trp Glu Lys Gly Glu Met Lys Asn Cys Ser Phe Asp Val Thr Thr     130 135 140 Asn Ile Arg Asp Lys Trp Gln Arg Glu Tyr Ala Leu Phe Tyr Lys Leu 145 150 155 160 Asp Val Val Pro Ile Asp Asn Asp Gly Asn Gly Asn Ser Ser Asn Asn                 165 170 175 Ala Thr Asp Asn Asn Asn Thr Thr Lys Tyr Thr Asn Tyr Arg Leu Ile             180 185 190 Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe         195 200 205 Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu     210 215 220 Lys Cys Lys Asp Glu Lys Phe Ser Gly Thr Gly Pro Cys Lys Asn Val 225 230 235 240 Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln                 245 250 255 Leu Leu Leu Asn Gly Ser Leu Ala Lys Glu Glu Ile Ile Ile Arg Ser             260 265 270 Glu Asn Leu Thr Asn Asn Ala Lys Thr Ile Ile Val Gln Leu Asn Glu         275 280 285 Ser Val Ser Ile Asn Cys Ile Arg Pro Asn Asn Asn Thr Arg Arg Gly     290 295 300 Ile Pro Ile Gly Pro Gly Gln Ala Phe Tyr Ala Thr Gly Asp Ile Ile 305 310 315 320 Gly Asp Ile Arg Lys Ala His Cys Ile Val Asn Ser Thr Gln Trp Asn                 325 330 335 Asn Thr Leu Ala Gln Val Ala Ile Lys Leu Asn Glu His Phe Pro Asn             340 345 350 Lys Thr Ile Val Phe Lys Gln Ser Ser Gly Gly Asp Pro Glu Ile Val         355 360 365 Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asp Ser Thr     370 375 380 Pro Leu Phe Asn Asn Thr Trp Asn Glu Thr His Phe Asn Asn Thr Trp 385 390 395 400 Asp Ser Ile Glu Lys Gly Lys Ile Ile Leu Gln Cys Arg Ile Lys Gln                 405 410 415 Ile Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro             420 425 430 Ile Arg Gly Leu Ile Asn Cys Thr Ser Asn Ile Thr Gly Leu Leu Leu         435 440 445 Thr Arg Asp Gly Gly Lys Lys Glu Asn Glu Ser Asp Thr Ile Glu Ile     450 455 460 Phe Arg Pro Gly Gly Gly Asp Met Arg Asn Asn Trp Arg Ser Glu Leu 465 470 475 480 Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val Ala Pro Thr                 485 490 495 Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg             500 505 <210> 63 <211> 1595 <212> DNA <213> Human immunodeficiency virus type 1 <400> 63 agaaagagca gaagacagtg gcaatgagag tgaaggagat catgaagaac tatcagaact 60 tatggagagg gggcatgatg ctccttggga tattcatgat ctgtagtgct acagaacaat 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga agcaaatacc actctatttt 180 gtgcatcaga tgctaaagca tataagacag aggtacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaag tattattgcc aaatatgaca gaagatttta 300 acatgtggaa aaataacatg gtagaacaga tgcatgagga tataatcagt ttgtgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cactctgtgt tactttaaaa tgcactgact 420 tgaatactac taatactatc aatagtagtg acttgatgga gaagggagaa ataaagaact 480 gctctttcaa tatcaccaca aacataagag ataagatgca gaaagactat gcgctttttt 540 atagacttga tgtagtacca atagataatg ataatactag ctataggttg ataagttgta 600 acacctcagt cattacacag gcctgcccaa aggtatcttt tgagccaatt cccatacatt 660 gttgtgcccc ggctggtttt gcgattctaa agtgtaaaga taagaatttc aatggaacag 720 gaacatgtaa aaatgtcagc acagtacagt gtacacatgg aattagacca gtagtatcaa 780 ctcaactgtt gttaaatggt agtctggcag aagaagaggt agtaattaga tctgccaatt 840 tcagtgacaa tgctaaaaac ataatagtac agctgaacga aactgtagaa attaattgta 900 caagacccaa caacaataca atgaaaagca tacatatagg actagggaga gcattttata 960 caacaggaca aataatagga gatataagaa aagcacattg tagcattaat atgacaaaat 1020 ggaataacac cttaatacag gtagctaaaa agttaggaga acaatttaag aataaaacaa 1080 tagtctttaa ccaatcctca ggaggggaca cagaaattgt aatgcacagc tttaattgtg 1140 gaggggaatt tttctactgc aatacaacac aactgtttaa tggtagttgg aatccaaatg 1200 gtacttggaa ttatgctggg gggtcaaacg acactatcac actcccatgc agaataaaac 1260 aaattataaa tatgtggcag gaagtaggaa aagcaatgta tgcccctccc gtcaaaggac 1320 aaatcagatg tgtatcaaac attacagggt tgatattaac aagagatggt ggtaatggtg 1380 gtaatggcac agacaacacc accgagatct ttaggcctgc aggaggaaat atgaaggaca 1440 attggagaag tgaattatat aaatataaag tagtaagaat tgaaccatta ggagtagcac 1500 ccactaaggc aaagagaaga gtggtacaaa gagaaaaaag agcagtggga atgggagctc 1560 tgttccttgg gttcttggga gcagcaggaa gcact 1595 <210> 64 <211> 479 <212> PRT <213> Human immunodeficiency virus type 1 <400> 64 Ser Ala Thr Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Lys Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Leu Leu Pro Asn Met Thr Glu Asp     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Lys Cys Thr Asp Leu Asn Thr Thr Asn Thr Ile             100 105 110 Asn Ser Ser Asp Leu Met Glu Lys Gly Glu Ile Lys Asn Cys Ser Phe         115 120 125 Asn Ile Thr Thr Asn Ile Arg Asp Lys Met Gln Lys Asp Tyr Ala Leu     130 135 140 Phe Tyr Arg Leu Asp Val Val Pro Ile Asp Asn Asp Asn Thr Ser Tyr 145 150 155 160 Arg Leu Ile Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys                 165 170 175 Val Ser Phe Glu Pro Ile Pro Ile His Cys Cys Ala Pro Ala Gly Phe             180 185 190 Ala Ile Leu Lys Cys Lys Asp Lys Asn Phe Asn Gly Thr Gly Thr Cys         195 200 205 Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val     210 215 220 Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val 225 230 235 240 Ile Arg Ser Ala Asn Phe Ser Asp Asn Ala Lys Asn Ile Ile Val Gln                 245 250 255 Leu Asn Glu Thr Val Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr             260 265 270 Met Lys Ser Ile His Ile Gly Leu Gly Arg Ala Phe Tyr Thr Thr Gly         275 280 285 Gln Ile Ile Gly Asp Ile Arg Lys Ala His Cys Ser Ile Asn Met Thr     290 295 300 Lys Trp Asn Asn Thr Leu Ile Gln Val Ala Lys Lys Leu Gly Glu Gln 305 310 315 320 Phe Lys Asn Lys Thr Ile Val Phe Asn Gln Ser Ser Gly Gly Asp Thr                 325 330 335 Glu Ile Val Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys             340 345 350 Asn Thr Thr Gln Leu Phe Asn Gly Ser Trp Asn Pro Asn Gly Thr Trp         355 360 365 Asn Tyr Ala Gly Gly Ser Asn Asp Thr Ile Thr Leu Pro Cys Arg Ile     370 375 380 Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala 385 390 395 400 Pro Pro Val Lys Gly Gln Ile Arg Cys Val Ser Asn Ile Thr Gly Leu                 405 410 415 Ile Leu Thr Arg Asp Gly Gly Asn Gly Gly Asn Gly Thr Asp Asn Thr             420 425 430 Thr Glu Ile Phe Arg Pro Ala Gly Gly Asn Met Lys Asp Asn Trp Arg         435 440 445 Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Pro Leu Gly Val     450 455 460 Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg 465 470 475 <210> 65 <211> 1592 <212> DNA <213> Human immunodeficiency virus type 1 <400> 65 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaggaat tgtcagcact 60 tatggagatg gggcaccatg ctccttggga tgttaatgat ctgtagtgct acagaacaat 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga agcaactacc accctatttt 180 gtgcatcaga tgctaaagca tatgatacag agagacataa tgtttgggcc acacatgcct 240 gtgtacccac agacccctgc ccacaagaag taggattggg aaatgtgaca gagtatttta 300 acatgtggaa aaataacatg gtagaacaga tgcatgagga tataatcagt ttatgggatc 360 aaagcctaaa gccatgtgta aaattaacac cactctgtgt tactttaaat tgtaatgcgg 420 gaaagtttaa ttatacgaat aatactgata cactgaaaga agaagtagga gaaataaaaa 480 actgctcttt caatatcacc acaagcataa gagataaggt aaagaaagaa tatgcatttt 540 ttaataaact tgatgtagta ccaatagata atgagaatga tagctatagg ttgataagtt 600 gtaacacctc agtcattact caggcctgtc caaaggtatc atttgagcca attcctatac 660 attattgtgc cccagctggt tttgcgattc taaggtgtaa taataagaca ttcaatggga 720 caggaccatg tacaaatgtc agtacagtac aatgtacaca tggaattagg ccagtagtgt 780 caacccaact gctgttaaat ggcagtctag cagaagagga ggtaatgatt aggtctgaga 840 acttcacgaa caatgctaaa accataatag tacagctgaa tgaatctgta gtaattaatt 900 gtacaagacc caacaacaat acaagaaaaa gtatacacat aggaccaggg agagcatttt 960 atacaacagg agagataata ggagatataa gaaaagcaca ttgtaacatt agtaaagcaa 1020 aatgggatag cactttaaaa caagtagtta caaaattaag agaacaatat ggaaataaaa 1080 caatagcctt taagaactcc tcaggagggg acccagaaat tgtaatgcac agttttaatt 1140 gtggagggga atttttctac tgtaatacaa caaagctatt taatagtact tggaatagga 1200 cagaggtaga tactattgaa ggaaatacca ctataaatat cacactccca tgtagaataa 1260 aacaaattat aaacatgtgg caggaagtag gaaaagcaat gtatgcccct cccatcagag 1320 gaccaattag ctgcacatca aatattacag ggctgctgtt aataagagat ggtggtacag 1380 acaatagcac gaacgacacc gagatcttca gacctggagg aggagatatg agggacaatt 1440 ggagaagtga attatacaaa tataaagtag taaaaattga accattagga atagcaccca 1500 ccaaggcaaa gagaagagtg gtgcagagag aaaaaagagc aataggaata ggagctgtgt 1560 tccttgggtt cttgggagca gcaggaagca ct 1592 <210> 66 <211> 478 <212> PRT <213> Human immunodeficiency virus type 1 <400> 66 Ser Ala Thr Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Arg His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Cys Pro Gln Glu Val Gly Leu Gly Asn Val Thr Glu Tyr     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Asn Ala Gly Lys Phe Asn Tyr Thr Asn             100 105 110 Asn Thr Asp Thr Leu Lys Glu Glu Val Gly Glu Ile Lys Asn Cys Ser         115 120 125 Phe Asn Ile Thr Thr Ser Ser Ile Arg Asp Lys Val Lys Lys Glu Tyr Ala     130 135 140 Phe Phe Asn Lys Leu Asp Val Val Pro Ile Asp Asn Glu Asn Asp Ser 145 150 155 160 Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro                 165 170 175 Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly             180 185 190 Phe Ala Ile Leu Arg Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro         195 200 205 Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val     210 215 220 Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val 225 230 235 240 Met Ile Arg Ser Glu Asn Phe Thr Asn Asn Ala Lys Thr Ile Ile Val                 245 250 255 Gln Leu Asn Glu Ser Val Val Ile Asn Cys Thr Arg Pro Asn Asn Asn             260 265 270 Thr Arg Lys Ser Ile His Ile Gly Pro Gly Arg Ala Phe Tyr Thr Thr         275 280 285 Gly Glu Ile Ile Gly Asp Ile Arg Lys Ala His Cys Asn Ile Ser Lys     290 295 300 Ala Lys Trp Asp Ser Thr Leu Lys Gln Val Val Thr Lys Leu Arg Glu 305 310 315 320 Gln Tyr Gly Asn Lys Thr Ile Ala Phe Lys Asn Ser Ser Gly Gly Asp                 325 330 335 Pro Glu Ile Val Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr             340 345 350 Cys Asn Thr Thr Lys Leu Phe Asn Ser Thr Trp Asn Arg Thr Glu Val         355 360 365 Asp Thr Ile Glu Gly Asn Thr Thr Ile Asn Ile Thr Leu Pro Cys Arg     370 375 380 Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr 385 390 395 400 Ala Pro Pro Ile Arg Gly Pro Ile Ser Cys Thr Ser Asn Ile Thr Gly                 405 410 415 Leu Leu Leu Ile Arg Asp Gly Gly Thr Asp Asn Ser Thr Asn Asp Thr             420 425 430 Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser         435 440 445 Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Ile Ala     450 455 460 Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg 465 470 475 <210> 67 <211> 1586 <212> DNA <213> Human immunodeficiency virus type 1 <400> 67 agaaagagca gaagacagtg gcaatgaaag tgacggggat catgaagaat tatcagcact 60 tatggagatg gggcatcatg ctccttggga tgttgatgat ctatagtact gcagaacaac 120 aattgtgggt cacagtctat tatggggtac ctgtgtggaa agaagcaact actactctat 180 tctgtgcatc agatgctaaa gcatatgata cagaggtaca taatgtttgg gccacacatg 240 cctgtgtacc cacagacccc aacccacaag aagtagtatt ggggaatgtg acagaaaatt 300 ttaacatgtg gaaaaataac atggtagaac agatgcatga ggatataatc agtttatggg 360 atcaaagcct aaaaccatgt gtaaaactaa ccccactctg tgttacttta aattgcactg 420 actgggataa aacgaattgc actaatgggg gagatattac tgctaatgag gaaaaaggag 480 aactaaaaaa ttgctctttc aatatcacca caaacataag agataagata cggaaagaat 540 atgcactttt ttataaattg gatgtagtac caatagataa tgataatact agttataggt 600 tgataaattg taacacctca gtcattacac aagcctgtcc aaaggtatcc tttgagccaa 660 ttcccataca ttattgtgcc ccggctggtt ttgcgattct aaagtgtaac aataagacgt 720 tcaatggaaa aggaccatgt aaaaatgtca gcacagtaca atgcacacat ggaattaggc 780 cagtagtgtc aactcaactg ctgttaaatg gcagtttagc agaagaagag gtagtagtta 840 gatctgccaa tttctcggac agtgccaaaa ccatcatagt acaactaaat gaatctgtag 900 taattaattg tacaagaccc aacaacaata caagaaaaag catacatata ggaccaggga 960 gagcatttta tgcaacagga gaaataatag gagatataag acaagcacat tgtaatctta 1020 gtctaacaaa atggaatcaa actttatatc aggtagttag aaaattaaaa gaacaattta 1080 agaataaaac aatagccttt aatcactcct caggagggga cccagaaatt gtaatgcaca 1140 gttttaattg tggaggagaa tttttctact gtaatacaac acaattattt aatagtactt 1200 ggtatactaa tggtacttgg agtgatactg gaagtaatga cacagtcaca ctcccatgca 1260 gaataaaaca aattataaac aggtggcaag aagtaggaaa agcaatgtat gcccctccca 1320 tcaaaggaca aattagatgc tcatcaaata ttacagggct gttattaaca agagatggtg 1380 gtagtagcaa aaacgagacc gaggtcttca gacctggagg aggagatatg agggacaatt 1440 ggagaagtga attatataaa tataaagtag taaaaattga accattagga gtagcaccca 1500 ccagggcaaa gagaagagtg gtgcagagag aaaaaagagg aataggagct gtgttccttg 1560 ggttcttggg agcagcagga agcact 1586 <210> 68 <211> 478 <212> PRT <213> Human immunodeficiency virus type 1 <400> 68 Ser Thr Ala Glu Gln Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro 1 5 10 15 Val Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys             20 25 30 Ala Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val         35 40 45 Pro Thr Asp Pro Asn Pro Gln Glu Val Val Leu Gly Asn Val Thr Glu     50 55 60 Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp 65 70 75 80 Ile Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr                 85 90 95 Pro Leu Cys Val Thr Leu Asn Cys Thr Asp Trp Asp Lys Thr Asn Cys             100 105 110 Thr Asn Gly Gly Asp Ile Thr Ala Asn Glu Glu Lys Gly Glu Leu Lys         115 120 125 Asn Cys Ser Phe Asn Ile Thr Thr Asn Ile Arg Asp Lys Ile Arg Lys     130 135 140 Glu Tyr Ala Leu Phe Tyr Lys Leu Asp Val Val Pro Ile Asp Asn Asp 145 150 155 160 Asn Thr Ser Tyr Arg Leu Ile Asn Cys Asn Thr Ser Val Ile Thr Gln                 165 170 175 Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala             180 185 190 Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly         195 200 205 Lys Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile     210 215 220 Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu 225 230 235 240 Glu Glu Val Val Val Arg Ser Ala Asn Phe Ser Asp Ser Ala Lys Thr                 245 250 255 Ile Ile Val Gln Leu Asn Glu Ser Val Val Ile Asn Cys Thr Arg Pro             260 265 270 Asn Asn Asn Thr Arg Lys Ser Ile His Ile Gly Pro Gly Arg Ala Phe         275 280 285 Tyr Ala Thr Gly Glu Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn     290 295 300 Leu Ser Leu Thr Lys Trp Asn Gln Thr Leu Tyr Gln Val Val Arg Lys 305 310 315 320 Leu Lys Glu Gln Phe Lys Asn Lys Thr Ile Ala Phe Asn His Ser Ser                 325 330 335 Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys Gly Gly Glu             340 345 350 Phe Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn Ser Thr Trp Tyr Thr         355 360 365 Asn Gly Thr Trp Ser Asp Thr Gly Ser Asn Asp Thr Val Thr Leu Pro     370 375 380 Cys Arg Ile Lys Gln Ile Ile Asn Arg Trp Gln Glu Val Gly Lys Ala 385 390 395 400 Met Tyr Ala Pro Pro Ile Lys Gly Gln Ile Arg Cys Ser Ser Asn Ile                 405 410 415 Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Ser Ser Lys Asn Glu Thr             420 425 430 Glu Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser         435 440 445 Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val Ala     450 455 460 Pro Thr Arg Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg 465 470 475 <210> 69 <211> 1628 <212> DNA <213> Human immunodeficiency virus type 1 <400> 69 agaaagagca gaagacagtg gcaatgagag cgaaggggac caagaagaat tggcagcagc 60 acttatggaa atggggcacg atgctccttg ggatgttaat gatctgtagt gctgcggaac 120 aatggtgggt cacagtctat tatggagtac ctgtgtggaa ggacgcaaat accactctat 180 tttgtgcatc agatgctaaa gcatatgata cagaggcaca taatgtctgg gccacacatg 240 cctgtgtacc cacagatccc aacccacaag aaatagtatt ggaaaatgtg acagaagatt 300 ttaacatgtg gaaaaataac atggcagacc agatgcatga ggatataatc agtttatggg 360 atcaaagcct aaagccatgt gtaaaattaa ctccgctctg tgttacttta aattgtactg 420 attggaatgg taatactact agcaatagta ctataaacaa caatactagt actaaggcag 480 aaatgaaaaa atgctctttt aatatcacca caagcataag agataaagtg acaaaggaat 540 atgcactgtt ttatagagtt gatgtagtac caatagataa agaaaataat aataccaatt 600 ataccaatta tagattaata aattgtaaca cctcagtcat tacacaagcc tgtccaaaga 660 catcctttga gccaattcct atacattatt gtgccccagc tggttttgca attctaaagt 720 gtaacaataa gacattcaca ggaaaaggac tctgtacaag ggttagcaca ttacaatgta 780 cacatggaat tagaccagta gtgtcaactc aactgctgtt aaatggcagt ctagcagaag 840 aggaggtagt aattagatgt gaaaatatca cagacaatgc taaaaccata atagtacagc 900 tgaatgaatc tgtagcaatt aattgtacaa gacctaataa caatacaaga aaaagtatac 960 ctataggacc agggagagca ttttatgcaa caggagatat agtaggaaat ataagacaag 1020 cacattgtaa ccttagtgga acagagtggg aaaaaacttt agggaaaata gttggggaat 1080 taagaaaaaa ttttgagaat aagacaataa tttttaatca atcctcagga ggggacccag 1140 aaattgtatc gcaccttttt aattgtggag gagaattttt ctattgtaac tcaacacaac 1200 tgtttaatag tacttggaat actactgcaa aaattgatgg ttctgggaat gttactggaa 1260 aggtaaatag cactatcaca ctccaatgta aaataagaca aattgtaaac ctgtggcagg 1320 aagtaggaaa agcaatgtat gcccctccca tcagtggaat aatttactgt tcatcaaata 1380 ttacagggct gatactgatg agagatggtg gtaatgatag tagcacgaat ggaaacgaga 1440 ccttcagacc tggaggggga aatatgaaag ataattggag aagtgaatta tataaatata 1500 aagtagtaaa aattgaacca ttaggactag cacccaccaa ggcaaagagg agagtggtgc 1560 aaagagaaaa aagagcagta ggaataggag ctatgttcct tgggttcttg ggagcagcag 1620 gaagcact 1628 <210> 70 <211> 489 <212> PRT <213> Human immunodeficiency virus type 1 <400> 70 Ser Ala Ala Glu Gln Trp Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Asp Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Ile Val Leu Glu Asn Val Thr Glu Asp     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Ala Asp Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Trp Asn Gly Asn Thr Thr Ser             100 105 110 Asn Ser Thr Ile Asn Asn Asn Thr Ser Thr Lys Ala Glu Met Lys Lys         115 120 125 Cys Ser Phe Asn Ile Thr Thr Ser Ile Arg Asp Lys Val Thr Lys Glu     130 135 140 Tyr Ala Leu Phe Tyr Arg Val Asp Val Val Pro Ile Asp Lys Glu Asn 145 150 155 160 Asn Asn Thr Asn Tyr Thr Asn Tyr Arg Leu Ile Asn Cys Asn Thr Ser                 165 170 175 Val Ile Thr Gln Ala Cys Pro Lys Thr Ser Phe Glu Pro Ile Pro Ile             180 185 190 His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys         195 200 205 Thr Phe Thr Gly Lys Gly Leu Cys Thr Arg Val Ser Thr Leu Gln Cys     210 215 220 Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly 225 230 235 240 Ser Leu Ala Glu Glu Glu Val Val Ile Arg Cys Glu Asn Ile Thr Asp                 245 250 255 Asn Ala Lys Thr Ile Ile Val Gln Leu Asn Glu Ser Val Ala Ile Asn             260 265 270 Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Pro Ile Gly Pro         275 280 285 Gly Arg Ala Phe Tyr Ala Thr Gly Asp Ile Val Gly Asn Ile Arg Gln     290 295 300 Ala His Cys Asn Leu Ser Gly Thr Glu Trp Glu Lys Thr Leu Gly Lys 305 310 315 320 Ile Val Gly Glu Leu Arg Lys Asn Phe Glu Asn Lys Thr Ile Ile Phe                 325 330 335 Asn Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Ser His Leu Phe Asn             340 345 350 Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr Gln Leu Phe Asn Ser         355 360 365 Thr Trp Asn Thr Thr Ala Lys Ile Asp Gly Ser Gly Asn Val Thr Gly     370 375 380 Lys Val Asn Ser Thr Ile Thr Leu Gln Cys Lys Ile Arg Gln Ile Val 385 390 395 400 Asn Leu Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser                 405 410 415 Gly Ile Ile Tyr Cys Ser Ser Asn Ile Thr Gly Leu Ile Leu Met Arg             420 425 430 Asp Gly Gly Asn Asp Ser Ser Thr Asn Gly Asn Glu Thr Phe Arg Pro         435 440 445 Gly Gly Gly Asn Met Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr     450 455 460 Lys Val Val Lys Ile Glu Pro Leu Gly Leu Ala Pro Thr Lys Ala Lys 465 470 475 480 Arg Arg Val Val Gln Arg Glu Lys Arg                 485 <210> 71 <211> 1622 <212> DNA <213> Human immunodeficiency virus type 1 <400> 71 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tggcggcgct 60 ggtggagatg gggcaccatg ctccttggga tgttaatgat ctgtagtgct acagaacaat 120 tgtgggttac agtctattat ggggtacctg tgtggaaaga agcaaccacc actctatttt 180 gtgcatcaga tgctaaagca tataatacag aggtacgtaa tgtatgggcc acacatgcct 240 gtgtgcccac aggccccaac ccacaagaaa tagtattggt aaatgtgaca gaagatttta 300 acatgtggaa aaatagcatg gtagaacaga tgcatgagga tataatcagt ttatgggatc 360 aaagcctaaa accttgtgta aaattaaccc cactctgtgt tactttaaac tgcactgatt 420 tgaggaatac tactaatagc actaatagtg acggggaaaa gatggagaga ggagaaataa 480 aaaactgctc tttcaatgtt accacaggca taagagataa ggttcagaga gaatatgcac 540 tcttttataa acttgatata gtaccaatag aggaaggtgg ggataatacc agctgtaggg 600 ataataccag ctataggttg ataagttgta atacctcagt cattacacaa gcctgtccaa 660 aggtatcctt tgagccaatt cccatacatt attgtgcccc agctggtttt gcgattctaa 720 agtgtaataa taagacgttc aatggaaaag gaccatgttc aaatgtcagc acagtacaat 780 gtacacatgg aattaggcca gtagtgtcaa ctcaactgct gttaaacggc agtctagcag 840 aaaaagaggt agtaattaga tctgaaaata tcacggacaa tactaaaaac ataatagtac 900 agttaaatga aactgtagaa attaattgta caagacccaa caacaataca agaaaaagta 960 tacatatagg accggggaga gcatttcatg caacaggaga aataatagga aatataagac 1020 aggcatattg taacattagt ggagcaaaat ggaataacac tttaaaacag atagtaaaaa 1080 gattaaaaga aaaatttccg aataagataa tagtctttaa tcactcctca ggaggggacc 1140 cagaaattgt aacacacagt tttaattgtg gaggggaatt tttctactgt aattcaacaa 1200 acctgtttaa tagtaattca acacaactgg ataattggac ttatactgaa gggtcaaatg 1260 acactgttat cacgctccca tgcagaataa aacaaattgt aaatatgtgg caggaagtag 1320 gaaaagcaat gtatgctcct cccatcagag gacaaattag atgttcttca aatattacag 1380 ggctgatatt aacaagagat ggtggtaata agactgacaa tgacaccacc gagaccttca 1440 gacctggagg aggaagcatg agggacaatt ggagaagtga attatataaa tataaaatag 1500 taaaggttga accactagga gtagcaccca ccaaggcaaa gaggagagtg gtgcagagag 1560 aaaaaagaac agtgggactg ggagccttgt ttcttgggtt cttgggagca gcaggaagca 1620 ct 1622 <210> 72 <211> 488 <212> PRT <213> Human immunodeficiency virus type 1 <400> 72 Ser Ala Thr Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asn Thr Glu Val Arg Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Gly Pro Asn Pro Gln Glu Ile Val Leu Val Asn Val Thr Glu Asp     50 55 60 Phe Asn Met Trp Lys Asn Ser Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Leu Arg Asn Thr Thr Asn Ser             100 105 110 Thr Asn Ser Asp Gly Glu Lys Met Glu Arg Gly Glu Ile Lys Asn Cys         115 120 125 Ser Phe Asn Val Thr Thr Gly Ile Arg Asp Lys Val Gln Arg Glu Tyr     130 135 140 Ala Leu Phe Tyr Lys Leu Asp Ile Val Pro Ile Glu Glu Gly Gly Asp 145 150 155 160 Asn Thr Ser Cys Arg Asp Asn Thr Ser Tyr Arg Leu Ile Ser Cys Asn                 165 170 175 Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile             180 185 190 Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn         195 200 205 Asn Lys Thr Phe Asn Gly Lys Gly Pro Cys Ser Asn Val Ser Thr Val     210 215 220 Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu 225 230 235 240 Asn Gly Ser Leu Ala Glu Lys Glu Val Val Ile Arg Ser Glu Asn Ile                 245 250 255 Thr Asp Asn Thr Lys Asn Ile Ile Val Gln Leu Asn Glu Thr Val Glu             260 265 270 Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile His Ile         275 280 285 Gly Pro Gly Arg Ala Phe His Ala Thr Gly Glu Ile Ile Gly Asn Ile     290 295 300 Arg Gln Ala Tyr Cys Asn Ile Ser Gly Ala Lys Trp Asn Asn Thr Leu 305 310 315 320 Lys Gln Ile Val Lys Arg Leu Lys Glu Lys Phe Pro Asn Lys Ile Ile                 325 330 335 Val Phe Asn His Ser Ser Gly Gly Asp Pro Glu Ile Val Thr His Ser             340 345 350 Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr Asn Leu Phe         355 360 365 Asn Ser Asn Ser Thr Gln Leu Asp Asn Trp Thr Tyr Thr Glu Gly Ser     370 375 380 Asn Asp Thr Val Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Val Asn 385 390 395 400 Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly                 405 410 415 Gln Ile Arg Cys Ser Ser Asn Ile Thr Gly Leu Ile Leu Thr Arg Asp             420 425 430 Gly Gly Asn Lys Thr Asp Asn Asp Thr Thr Glu Thr Phe Arg Pro Gly         435 440 445 Gly Gly Ser Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys     450 455 460 Ile Val Lys Val Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg 465 470 475 480 Arg Val Val Gln Arg Glu Lys Arg                 485 <210> 73 <211> 1622 <212> DNA <213> Human immunodeficiency virus type 1 <400> 73 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tatcagcact 60 tgtggagagg ggacaacttg tggagagggg gcatcatgct ccttgggata ttgatgatct 120 gtagtgctac agaaaaattg tgggtcacag tctattatgg ggtacctgtg tggaaaaatg 180 caaacaccac tctattttgt gcatcagatg ctaaagcata tgatacagag gtacataatg 240 tttgggccac acacgcctgt gtacccacag accccagccc acgagaatta atattggaaa 300 atgtgacaga agactttgac atatggaaaa ataacatggt agaacagatg caagaggata 360 taatcagttt atgggatcaa agcctaaagc catgtgtaaa attaacccct ctctgtgtta 420 ctttagaatg caagaatgcc actaaaatta gtaatagcag tgaaattgga gaaatgaaaa 480 actgctcttt taatgttacc acagacagga gagataaggt gaaaacagaa tatgcacttt 540 tttataacct tgatataata caaatagagg aggagaatac cagcagctgc agtaatacca 600 gcagctacag gttgataagt tgtaacacct caacccttac acaggcctgt ccaaagatat 660 cctttgagcc aattcccata cattattgtg ccccggctgg ttttgcaatt ctaaagtgta 720 ataataaaac attcgatgga aaaggatcat gtaaaaatgt cagcacagta caatgtacac 780 atggaattaa gccagtagta tcaactcaac tgctgctaaa cggcagtcta gcagaagaag 840 aggtagtaat tagatctgct aatctctcag acaatgctaa aaccataata gtacagctga 900 acatgtctgt acaaattaat tgtacaagac ccaacaacaa tacaagaaga ggtatacatt 960 taggaccagg gagagccttt tatggaacag acataatagg agatataaga caagcacatt 1020 gtaacattag tggaaaacaa tggaattaca ctttacaaca gatagttaaa aaattcagaa 1080 aacaatttga gaatagcaca gtgatcttta acagatcctc aggaggggac ccagaaattg 1140 taatgcacag ttttaattgt ggaggggaat ttttctactg taatacaaca gaactgttta 1200 atagtacttg gaacagtagt catcctttgg atgatacttg gcctcctttg gataatacaa 1260 gtgacactac tatcacactc ccatgcagaa taaaacaaat tataaacatg tggcaggaag 1320 taggaaaagc aatgtatgcc cctcccatca aaggaccaat tagatgtgaa tcaaatatta 1380 cagggctgct attaacaaga gatggtggcg ataccaatac cactaacggg actgagacct 1440 tcagacctgg aggaggagat atgagggaca attggagaag tgaattatat aaatataaag 1500 tagtaagaat taaaccatta ggaatagcac ccaccaaggc acagagaaga gtggtgcaaa 1560 gagaaaaaag agcagcacta ggagctatgt tccttgggtt cttgggagca gcaggaagca 1620 ct 1622 <210> 74 <211> 483 <212> PRT <213> Human immunodeficiency virus type 1 <400> 74 Ser Ala Thr Glu Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Asn Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Ser Pro Arg Glu Leu Ile Leu Glu Asn Val Thr Glu Asp     50 55 60 Phe Asp Ile Trp Lys Asn Asn Met Val Glu Gln Met Gln Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Glu Cys Lys Asn Ala Thr Lys Ile Ser Asn Ser             100 105 110 Ser Glu Ile Gly Glu Met Lys Asn Cys Ser Phe Asn Val Thr Thr Asp         115 120 125 Arg Arg Asp Lys Val Lys Thr Glu Tyr Ala Leu Phe Tyr Asn Leu Asp     130 135 140 Ile Ile Gln Ile Glu Glu Glu Asn Thr Ser Ser Cys Ser Asn Thr Ser 145 150 155 160 Ser Tyr Arg Leu Ile Ser Cys Asn Thr Ser Thr Leu Thr Gln Ala Cys                 165 170 175 Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala             180 185 190 Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asp Gly Lys Gly         195 200 205 Ser Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro     210 215 220 Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu 225 230 235 240 Val Val Ile Arg Ser Ala Asn Leu Ser Asp Asn Ala Lys Thr Ile Ile                 245 250 255 Val Gln Leu Asn Met Ser Val Gln Ile Asn Cys Thr Arg Pro Asn Asn             260 265 270 Asn Thr Arg Arg Gly Ile His Leu Gly Pro Gly Arg Ala Phe Tyr Gly         275 280 285 Thr Asp Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn Ile Ser Gly     290 295 300 Lys Gln Trp Asn Tyr Thr Leu Gln Gln Ile Val Lys Lys Phe Arg Lys 305 310 315 320 Gln Phe Glu Asn Ser Thr Val Ile Phe Asn Arg Ser Ser Gly Gly Asp                 325 330 335 Pro Glu Ile Val Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr             340 345 350 Cys Asn Thr Thr Glu Leu Phe Asn Ser Thr Trp Asn Ser Ser His Pro         355 360 365 Leu Asp Asp Thr Trp Pro Pro Leu Asp Asn Thr Ser Asp Thr Thr Ile     370 375 380 Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val 385 390 395 400 Gly Lys Ala Met Tyr Ala Pro Pro Ile Lys Gly Pro Ile Arg Cys Glu                 405 410 415 Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asp Thr Asn             420 425 430 Thr Thr Asn Gly Thr Glu Thr Phe Arg Pro Gly Gly Gly Asp Met Arg         435 440 445 Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile Lys     450 455 460 Pro Leu Gly Ile Ala Pro Thr Lys Ala Gln Arg Arg Val Val Gln Arg 465 470 475 480 Glu lys arg              <210> 75 <211> 1574 <212> DNA <213> Human immunodeficiency virus type 1 <400> 75 agaaagagca gaagacagtg gcaatgacag tgatggggat caggaggaat tatcaatgct 60 tgtggaaatg gggcatgacg ctccttggga tgttgatgat ctgtagtgct gcacaattgt 120 gggtcacagt ctgttatggg gtaccggtgt ggaaagaagc aaccaccact ctattttgtg 180 catcagatgc taaagcatat gacacagagg tacataatgt ttgggccaca catgcctgtg 240 tacccacaga ccccaatcca ctagaattaa aattggataa tgtgacagaa aattttaaca 300 tgtggaaaaa taacatggta gaacaaatgc atgaggatat aatcagttta tgggatcaaa 360 gcctaaagcc atgtgtaaaa ttaaccccac tctgtgttac tttaaattgc actgactact 420 cgaagaatgg tactaataac actgctaata atgaaggaga aatgaaaaac tgctctttta 480 atatcaccac aaacataaga gataagatgc agaatgaata cgcacttttt tataaacatg 540 atatggtatc aatagataat agtagtacta gctataggtt gacaagttgt aacacctcag 600 tcattacaca ggcctgtcca aagataacct ttgaaccaat tcctatacat tattgtaccc 660 cggctggttt tgcgctttta aagtgtaata ataaaacgtt caatggaaca ggaccatgta 720 aaaatgtcag cacagtacaa tgtacacatg gaattaggcc agtagtttca actcaactgc 780 tgttaaatgg cagtctagca gaagaagagg tagtaattag atctgaaaat ttcacgaaca 840 atgcaaaaat cataatagta cagctaaatg aaactataca aattaattgt acaagaccca 900 acaacaatac aagaaaaagt atacatatag caccagggag agcattttat gcaacaggag 960 aaataatagg agatataaga caagcacatt gtaacattag cagagcaaaa tggaacaacg 1020 ctttaaaaca gatagttgaa aaattaagag aacaatttaa gaataaaaca atagaattta 1080 agtcatcctc aggaggggac ccagaaattg taatgcacag tttcaattgt ggaggggaat 1140 ttttctactg taattcaaca aaactgttta atagtatttg gtatccgaat ggtactgaag 1200 ggtcaaataa cactgaagga aatgacccaa tcacactccc atgcagaata agacaaattg 1260 taaacagatg gcaggaagta ggaaaagcaa tgtatgcccc tcccatcagg ggaccaatta 1320 gatgttcatc aaatattaca gggctgctat taacaagaga tggtggtgct aataatactg 1380 ataatgagac cttcagacct ggaggaggag atatgaggga caattggaga agtgaattat 1440 ataaatataa agtagtaaga attgaaccat taggaatagc gcccactacg gcaaggagaa 1500 gagtggtgca aagagaaaaa agggcagcca taggagctat gatccttggg ttcttgggag 1560 cagcaggaag cact 1574 <210> 76 <211> 473 <212> PRT <213> Human immunodeficiency virus type 1 <400> 76 Ser Ala Ala Gln Leu Trp Val Thr Val Cys Tyr Gly Val Pro Val Trp 1 5 10 15 Lys Glu Ala Thr Thr Thr Le Le Phe Cys Ala Ser Asp Ala Lys Ala Tyr             20 25 30 Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr         35 40 45 Asp Pro Asn Pro Leu Glu Leu Lys Leu Asp Asn Val Thr Glu Asn Phe     50 55 60 Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile 65 70 75 80 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu                 85 90 95 Cys Val Thr Leu Asn Cys Thr Asp Tyr Ser Lys Asn Gly Thr Asn Asn             100 105 110 Thr Ala Asn Asn Glu Gly Glu Met Lys Asn Cys Ser Phe Asn Ile Thr         115 120 125 Thr Asn Ile Arg Asp Lys Met Gln Asn Glu Tyr Ala Leu Phe Tyr Lys     130 135 140 His Asp Met Val Ser Ile Asp Asn Ser Ser Thr Ser Tyr Arg Leu Thr 145 150 155 160 Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Ile Thr Phe                 165 170 175 Glu Pro Ile Pro Ile His Tyr Cys Thr Pro Ala Gly Phe Ala Leu Leu             180 185 190 Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys Lys Asn Val         195 200 205 Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln     210 215 220 Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser 225 230 235 240 Glu Asn Phe Thr Asn Asn Ala Lys Ile Ile Ile Val Gln Leu Asn Glu                 245 250 255 Thr Ile Gln Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser             260 265 270 Ile His Ile Ala Pro Gly Arg Ala Phe Tyr Ala Thr Gly Glu Ile Ile         275 280 285 Gly Asp Ile Arg Gln Ala His Cys Asn Ile Ser Arg Ala Lys Trp Asn     290 295 300 Asn Ala Leu Lys Gln Ile Val Glu Lys Leu Arg Glu Gln Phe Lys Asn 305 310 315 320 Lys Thr Ile Glu Phe Lys Ser Ser Ser Gly Gly Asp Pro Glu Ile Val                 325 330 335 Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr             340 345 350 Lys Leu Phe Asn Ser Ile Trp Tyr Pro Asn Gly Thr Glu Gly Ser Asn         355 360 365 Asn Thr Glu Gly Asn Asp Pro Ile Thr Leu Pro Cys Arg Ile Arg Gln     370 375 380 Ile Val Asn Arg Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro 385 390 395 400 Ile Arg Gly Pro Ile Arg Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu                 405 410 415 Thr Arg Asp Gly Gly Ala Asn Asn Thr Asp Asn Glu Thr Phe Arg Pro             420 425 430 Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr         435 440 445 Lys Val Val Arg Ile Glu Pro Leu Gly Ile Ala Pro Thr Thr Ala Arg     450 455 460 Arg Arg Val Val Gln Arg Glu Lys Arg 465 470 <210> 77 <211> 1610 <212> DNA <213> Human immunodeficiency virus type 1 <400> 77 agaaagagca gaagacagtg gcaatgaaag tgaaggggat caggaagaat tgtcagcgct 60 ggtggatagg gggcatcttg ctccttggaa tgttgatgat ctgtagtgct gcagaacaat 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga agcaaacatc actctatttt 180 gtgcatcaga tgctaaggga tatgatacag aagcacataa tgtctgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagagg tagcattgac aaatgtgaca gaaaacttta 300 acatgtggaa aaataacatg gtagaacaaa tgcatgagga tataattagt ttatgggatc 360 aaagcttaaa gccatgtgta aaattaaccc cactctgtgt tactttagat tgcaatgata 420 ctaatataaa tgtaactagc aaaaatgaga caatgatgga gcaaggagaa gcaaaaaact 480 gctctttcaa tatcaccaca aatttaagag ataaggtgca gaaagaatat tcagtttttt 540 ataaacttga tgtagtacca atagaagagg agaaaaataa tagtattaac aatagatata 600 ggttgataag ttgtaacacc tcagtcatta cacaagcctg tccaaagata tcctttgaac 660 caattcccat acattattgt gccccggctg gttttgcgat tctgaagtgt aacaataaga 720 cattcagtgg aaaaggacca tgcacaaatg tcagcacagt acaatgcaca catggaatta 780 ggccagtagt atcaactcaa ctgctgttaa atggcagcct agcagaagga gagatagtaa 840 ttagatctga caatttcaca gacaatacaa aaaccataat agtacagctg aatacatctg 900 tagcaattaa ttgtacaaga cccaacaaca atacaagaag aagtataact ataggaccag 960 ggagagcatt ttatgcaaca gacataatag gagatataag acaagcacat tgtaacatta 1020 gtagaacaca atggaataac actttaaaac aggtagctag aaaattaagt gaacaattta 1080 atgcaacaat agtttttaat aaatcctcag gaggggaccc agaaattgta atgcacagtt 1140 ttaattgtgg aggggaattt ttctactgta atacaacaca actgtttaat agtatttggt 1200 gtcctaataa tactggagag tcaaatagca ctaacaatga gacaatcata ctcccatgca 1260 gattaaaaca atttataaac atgtggcagg aggtaggaaa agcaatgtat gcccctccca 1320 tcagaggata cattaactgt tcatcaaata ttacggggct gctattaaca agagatggtg 1380 gtggtgataa taaaaacacg agtccagaga acaagacaga gaccttcaga cctggaggag 1440 gaaatatgaa ggacaattgg agaagtgaac tgtataaata taaagtagta agaattgaac 1500 cattaggagt agcacccacc aaggcaaaga gaagagtggt gcagagagaa aaaagagcag 1560 tgggaatagg agctatgttc cttgggttct tgggagcagc aggaagcact 1610 <210> 78 <211> 484 <212> PRT <213> Human immunodeficiency virus type 1 <400> 78 Ser Ala Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Asn Ile Thr Leu Phe Cys Ala Ser Asp Ala Lys Gly             20 25 30 Tyr Asp Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Ala Leu Thr Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asp Cys Asn Asp Thr Asn Ile Asn Val Thr Ser             100 105 110 Lys Asn Glu Thr Met Met Glu Gln Gly Glu Ala Lys Asn Cys Ser Phe         115 120 125 Asn Ile Thr Thr Asn Leu Arg Asp Lys Val Gln Lys Glu Tyr Ser Val     130 135 140 Phe Tyr Lys Leu Asp Val Val Pro Ile Glu Glu Glu Lys Asn Asn Ser 145 150 155 160 Ile Asn Asn Arg Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val Ile Thr                 165 170 175 Gln Ala Cys Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile His Tyr Cys             180 185 190 Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Ser         195 200 205 Gly Lys Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly     210 215 220 Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala 225 230 235 240 Glu Gly Glu Ile Val Ile Arg Ser Asp Asn Phe Thr Asp Asn Thr Lys                 245 250 255 Thr Ile Ile Val Gln Leu Asn Thr Ser Val Ala Ile Asn Cys Thr Arg             260 265 270 Pro Asn Asn Asn Thr Arg Arg Ser Ile Thr Ile Gly Pro Gly Arg Ala         275 280 285 Phe Tyr Ala Thr Asp Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn     290 295 300 Ile Ser Arg Thr Gln Trp Asn Asn Thr Leu Lys Gln Val Ala Arg Lys 305 310 315 320 Leu Ser Glu Gln Phe Asn Ala Thr Ile Val Phe Asn Lys Ser Ser Gly                 325 330 335 Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys Gly Gly Glu Phe             340 345 350 Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn Ser Ile Trp Cys Pro Asn         355 360 365 Asn Thr Gly Glu Ser Asn Ser Thr Asn Asn Glu Thr Ile Ile Leu Pro     370 375 380 Cys Arg Leu Lys Gln Phe Ile Asn Met Trp Gln Glu Val Gly Lys Ala 385 390 395 400 Met Tyr Ala Pro Pro Ile Arg Gly Tyr Ile Asn Cys Ser Ser Asn Ile                 405 410 415 Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Gly Asp Asn Lys Asn Thr             420 425 430 Ser Pro Glu Asn Lys Thr Glu Thr Phe Arg Pro Gly Gly Gly Asn Met         435 440 445 Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile     450 455 460 Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln 465 470 475 480 Arg Glu Lys Arg                  <210> 79 <211> 1607 <212> DNA <213> Human immunodeficiency virus type 1 <400> 79 agaaagagca gaagacagtg gcaatgaaag cgaaggggac caggaagaat tatcagcact 60 tgtggagatg gggtaccatg ctccttggga tgttgatgat ctgtagtgct acagagcaat 120 tgtgggtaac agtctattat ggggtacctg tgtggaaaga agcaaaaacc actctatttt 180 gtgcatcaga tgctaaagca tatgatacag agatgcataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaaa tagtattgga aaatgtgaca gaaaatttta 300 acatgtggaa aaataacatg gtagatcaga tgcaggagga tgtaatcagt ctatgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cactctgtgt tactttaaat tgcaatgata 420 cattgaggaa tgataatagc actaagaata atagtagtac tggttgggaa aagatggaga 480 aaggagaaat aaaaaattgc tctttcagtg ccaccacaac cgtgaaagat aagacacaga 540 aacaatatgc acttttttat aatcttgata tagtacatac aaatgatggt ggtaatagta 600 gctatatgtt aagaagttgt aacacctcag tcattacaca ggcctgtcca aaggtatcat 660 ttgagccaat tcccatacat tattgtgccc cggctggttt tgcgattcta aagtgtaatg 720 ataagaagtt caatgggaca ggaccatgta aaaatgtcag cacagtacaa tgtacacatg 780 gaattaggcc agtagtgtca actcaactgc tattaaatgg cagtctagca gaagaagagg 840 tagtaattag atctagcaat ttaacggaca atactaaaac cataatagta cagctgaagg 900 aatctgtaaa aattaattgt acaagaccca acaacaatac aagaaaaagt atatctatag 960 gaccagggag cgcattttat gcaacaggag acataatagg agatataaga caagcacatt 1020 gcaaccttag taaaacagaa tggggggaaa ctttaagaca gatagctaca aaattaagag 1080 aacaatttaa taataaaaca ataatcttta atagctcctc aggaggggac ccagaaattg 1140 taatgcacag ttttaattgt ggaggggaat ttttctactg taatacaaca aaactgttta 1200 atggtacttg gaatggtact tggaagaatg gtacttggag tacaaatgat actgaaaatg 1260 atactatcat actcccatgt agaataaaac aaattataaa catgtggcag gaagtaggaa 1320 aagcaatgtg tgcccctccc atcagaggac aaattaactg ctcatcacag attacagggc 1380 tgctattaac aagagatggt ggagataacc ctaaaaatga aaccttcaga cctggaggag 1440 gagatatgag ggacaattgg agaagtgaat tatataaata taaagtagta aaaattgaac 1500 cattaggaat agcacctacc agggcaaaga gaagagtggt gcagagagaa aaaagagcag 1560 caataggagc tatgatcctt gggttcttgg gagcagcagg aagcact 1607 <210> 80 <211> 484 <212> PRT <213> Human immunodeficiency virus type 1 <400> 80 Ser Ala Thr Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Lys Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Met His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Ile Val Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Asp Gln Met Gln Glu Asp Val 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Asn Asp Thr Leu Arg Asn Asp Asn Ser             100 105 110 Thr Lys Asn Asn Ser Ser Thr Gly Trp Glu Lys Met Glu Lys Gly Glu         115 120 125 Ile Lys Asn Cys Ser Phe Ser Ala Thr Thr Thr Thr Val Lys Asp Lys Thr     130 135 140 Gln Lys Gln Tyr Ala Leu Phe Tyr Asn Leu Asp Ile Val His Thr Asn 145 150 155 160 Asp Gly Gly Asn Ser Ser Tyr Met Leu Arg Ser Cys Asn Thr Ser Val                 165 170 175 Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His             180 185 190 Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Lys         195 200 205 Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys Thr     210 215 220 His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser 225 230 235 240 Leu Ala Glu Glu Glu Val Val Ile Arg Ser Ser Asn Leu Thr Asp Asn                 245 250 255 Thr Lys Thr Ile Ile Val Gln Leu Lys Glu Ser Val Lys Ile Asn Cys             260 265 270 Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Ser Ile Gly Pro Gly         275 280 285 Ser Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala     290 295 300 His Cys Asn Leu Ser Lys Thr Glu Trp Gly Glu Thr Leu Arg Gln Ile 305 310 315 320 Ala Thr Lys Leu Arg Glu Gln Phe Asn Asn Lys Thr Ile Ile Phe Asn                 325 330 335 Ser Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys             340 345 350 Gly Gly Glu Phe Phe Tyr Cys Asn Thr Thr Lys Leu Phe Asn Gly Thr         355 360 365 Trp Asn Gly Thr Trp Lys Asn Gly Thr Trp Ser Thr Asn Asp Thr Glu     370 375 380 Asn Asp Thr Ile Ile Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met 385 390 395 400 Trp Gln Glu Val Gly Lys Ala Met Cys Ala Pro Pro Ile Arg Gly Gln                 405 410 415 Ile Asn Cys Ser Ser Gln Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly             420 425 430 Gly Asp Asn Pro Lys Asn Glu Thr Phe Arg Pro Gly Gly Gly Asp Met         435 440 445 Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile     450 455 460 Glu Pro Leu Gly Ile Ala Pro Thr Arg Ala Lys Arg Arg Val Val Gln 465 470 475 480 Arg Glu Lys Arg                  <210> 81 <211> 1580 <212> DNA <213> Human immunodeficiency virus type 1 <400> 81 agaaagagca gaagacagtg gcaatgagag tgagggggat tatgaggaat tatcagcact 60 tgtggagatg gggcatgacg ctccttggga tgttaatgat cagtagtgct aatgaacaat 120 tgtgggtcac agtctgttat ggggtacctg tgtggaaaga agcaaccact actttatttt 180 gtgcatcaga tgctaaagca tatgctgcag agaaacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaag tagtaataaa tgtgacagaa aattttaaca 300 tgtggaaaaa taacatggta gagcagatgc atgaagatgt aactagttta tgggaccaaa 360 gcctaaagcc atgtgtaaaa ttaacccctc tctgtgttac tttaaattgc actgactatg 420 aggggaataa tatcactagt gggaataaga caggagaaat aaaaaactgc tctttcgaga 480 tcaccacaaa catgagagat aagatacaga aaacatatgc acttttttat agacttgatg 540 tagaaccaat aaatgatgat aatgttactt ataggttgat aagctgtaat acctcagtca 600 ttacacaagc ctgtccaaag gtaacctttg agccaattcc catacattat tgtgccccgg 660 ctggctttgc gattgtaaag tgtaacaata aaacgttcaa tggaacagga ccatgtaaaa 720 atgttagcac agtacaatgt acacatggaa ttaggccagt agtatcaact caactgctgt 780 taaatggcag tctagcggaa gaagagacaa tgattagatc tgagaatttc tcggacaatg 840 ctaaaatcat aatagtacag ctgaataaat ctgtaaaaat taattgtaca agacccaaca 900 ataatacaat aaaaggtata catataggac cagggagagc attttataca acaggacaaa 960 taataggaga cataagacaa gcatattgta ccattaataa aacagaatgg aataacactt 1020 tatcacagat agctaaaaaa ttaagtagac aatttgagaa taaaacaata gcctttaggc 1080 caccctcagg aggggaccca gaaattgtaa tgcacagttt taattgtgga ggggaatttt 1140 tctattgtaa tacaacacaa ctgtttaata gtaattggac tactaatgga gagtcaaatt 1200 acacaacggg aaacaatgag acaattatca cactcccatg cagaataaaa caatttataa 1260 acatgtggca ggaagtagga aaagcaatgt atgcccctcc cattagtgga ataattaatt 1320 gcttatcaaa tattacaggg ctgctattaa caagagatgg tggtaatagt agcagcgcca 1380 acagcaccga gatcttcaga cctggaggag gggatatgag ggataattgg agaagtgaac 1440 tatataaata taaagtagta caaattgaac cattaggatt agcacccacc aaggcaaaga 1500 gaagagtggt gcagagagaa aaaagagcag tgggactagg agctgtgttc cttgggttct 1560 tgggagcagc aggaagcact 1580 <210> 82 <211> 474 <212> PRT <213> Human immunodeficiency virus type 1 <400> 82 Ser Ala Asn Glu Gln Leu Trp Val Thr Val Cys Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Ala Ala Glu Lys His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Ile Asn Val Thr Glu Asn Phe     50 55 60 Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Val Thr 65 70 75 80 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu                 85 90 95 Cys Val Thr Leu Asn Cys Thr Asp Tyr Glu Gly Asn Asn Ile Thr Ser             100 105 110 Gly Asn Lys Thr Gly Glu Ile Lys Asn Cys Ser Phe Glu Ile Thr Thr         115 120 125 Asn Met Arg Asp Lys Ile Gln Lys Thr Tyr Ala Leu Phe Tyr Arg Leu     130 135 140 Asp Val Glu Pro Ile Asn Asp Asp Asn Val Thr Tyr Arg Leu Ile Ser 145 150 155 160 Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Thr Phe Glu                 165 170 175 Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Val Lys             180 185 190 Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser         195 200 205 Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu     210 215 220 Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Thr Met Ile Arg Ser Glu 225 230 235 240 Asn Phe Ser Asp Asn Ala Lys Ile Ile Ile Val Gln Leu Asn Lys Ser                 245 250 255 Val Lys Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Ile Lys Gly Ile             260 265 270 His Ile Gly Pro Gly Arg Ala Phe Tyr Thr Thr Gly Gln Ile Ile Gly         275 280 285 Asp Ile Arg Gln Ala Tyr Cys Thr Ile Asn Lys Thr Glu Trp Asn Asn     290 295 300 Thr Leu Ser Gln Ile Ala Lys Lys Leu Ser Arg Gln Phe Glu Asn Lys 305 310 315 320 Thr Ile Ala Phe Arg Pro Pro Ser Gly Gly Asp Pro Glu Ile Val Met                 325 330 335 His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gln             340 345 350 Leu Phe Asn Ser Asn Trp Thr Thr Asn Gly Glu Ser Asn Tyr Thr Thr         355 360 365 Gly Asn Asn Glu Thr Ile Ile Thr Leu Pro Cys Arg Ile Lys Gln Phe     370 375 380 Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile 385 390 395 400 Ser Gly Ile Ile Asn Cys Leu Ser Asn Ile Thr Gly Leu Leu Leu Thr                 405 410 415 Arg Asp Gly Gly Asn Ser Ser Ser Ala Asn Ser Thr Glu Ile Phe Arg             420 425 430 Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys         435 440 445 Tyr Lys Val Val Gln Ile Glu Pro Leu Gly Leu Ala Pro Thr Lys Ala     450 455 460 Lys Arg Arg Val Val Gln Arg Glu Lys Arg 465 470 <210> 83 <211> 1643 <212> DNA <213> Human immunodeficiency virus type 1 <400> 83 agaaagagca gaagacagtg gcaatgagag tgaaggagat caggaagaat tgtcagaaat 60 tctggaaatg gggcaccttg ctccttggga tgttaatgat gatctgtaga gctgcagagg 120 attcgtgggt cacagtctat tatggggtac ctgtgtggaa ggaagcaacc accactctat 180 tttgtgcatc agatgctaaa gcatatgaca cagaggtaca taatgtttgg gccacacatg 240 cctgtgtacc cacagaccct aacccacaag aagtagtatt ggaaaatgtg acagaaaatt 300 tcaatgcgtg gaaaaataat atggtagaac agatgcatga ggatataatc agtttatggg 360 atcaaagcct aaagccatgt gtaaaattaa cccctctttg tgttactcta aattgcactg 420 atgtgagaaa taatgctacc aatactacta ataccaatag tactaatacc tatagtacta 480 acatagaaaa gatgaaagaa ggagaaataa aaaactgctc tttcaatacc accccaagca 540 taacagacaa gatgcagaag gcatatgcat tgttttataa gcttgatata gtacagataa 600 ataatgataa taaagataat accagctata gattgataag ttgtaatacc tcagtcatta 660 cacaggcctg tccaaaggca tcctttgagc caattcccat acattattgt gccccagctg 720 gttttgcgat tctaaagtgt aatgataaga agttcaatgg aacaggacca tgcaaaaatg 780 tcagcacagt acaatgtaca catggaatta ggccagtagt atcaacccaa ctgctgttaa 840 atggcagtct agcagaagaa gaggtagtaa ttagatctga aaatttcaca aacaatgcta 900 aaaccataat agtacagctg aatgagactg tacatattaa ttgtacaaga cccaacaaca 960 atacaagaaa aagtataggt ataggaccag ggagaacatt ttttgcaaca ggggaaataa 1020 taggagacat aagacaagca cattgtaaca ttagtagaaa caactggaat aaaactttag 1080 aaagggtagt taaaaaatta agagaacaat ttgggaacaa caaaacaatt gtttttaatc 1140 aatcctcagg aggggaccca gaaattgtga tgcacagttt taattgtaga ggagaatttt 1200 tctactgtaa tacaacacaa ctgtttaata gtacttggaa tgctaatagt acttggaatg 1260 ctaacgagaa tactactgga atgccaagtg acaatatcac actcccctgc agaataaaac 1320 aagttataaa catgtggcag gaagtaggaa aagcaatgta tgcccctccc attaaaggac 1380 caattaagtg ttcatcaaat attacaggac tgctattaac aagggatggt ggtgtgaaca 1440 attctgaaac tgagaccttc agacctggag gaggagatat gaggaacaat tggagatgtg 1500 gattatataa atataaagta gtaaaaattg agccattagg agtagcaccc accagggcaa 1560 agagaagagt ggtgcaaaga gaaaaaagag cagtgggact aggagctatg ttccttgggt 1620 tcttgggagc agcaggaagc act 1643 <210> 84 <211> 494 <212> PRT <213> Human immunodeficiency virus type 1 <400> 84 Arg Ala Ala Glu Asp Ser Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Ala Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Val Arg Asn Asla Ala Thr Asn             100 105 110 Thr Thr Asn Thr Asn Ser Thr Asn Thr Tyr Ser Thr Asn Ile Glu Lys         115 120 125 Met Lys Glu Gly Glu Ile Lys Asn Cys Ser Phe Asn Thr Thr Pro Ser     130 135 140 Ile Thr Asp Lys Met Gln Lys Ala Tyr Ala Leu Phe Tyr Lys Leu Asp 145 150 155 160 Ile Val Gln Ile Asn Asn Asp Asn Lys Asp Asn Thr Ser Tyr Arg Leu                 165 170 175 Ile Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Ala Ser             180 185 190 Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile         195 200 205 Leu Lys Cys Asn Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn     210 215 220 Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr 225 230 235 240 Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg                 245 250 255 Ser Glu Asn Phe Thr Asn Asn Ala Lys Thr Ile Ile Val Gln Leu Asn             260 265 270 Glu Thr Val His Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys         275 280 285 Ser Ile Gly Ile Gly Pro Gly Arg Thr Phe Phe Ala Thr Gly Glu Ile     290 295 300 Ile Gly Asp Ile Arg Gln Ala His Cys Asn Ile Ser Arg Asn Asn Trp 305 310 315 320 Asn Lys Thr Leu Glu Arg Val Val Lys Lys Leu Arg Glu Gln Phe Gly                 325 330 335 Asn Asn Lys Thr Ile Val Phe Asn Gln Ser Ser Gly Gly Asp Pro Glu             340 345 350 Ile Val Met His Ser Phe Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn         355 360 365 Thr Thr Gln Leu Phe Asn Ser Thr Trp Asn Ala Asn Ser Thr Trp Asn     370 375 380 Ala Asn Glu Asn Thr Thr Gly Met Pro Ser Asp Asn Ile Thr Leu Pro 385 390 395 400 Cys Arg Ile Lys Gln Val Ile Asn Met Trp Gln Glu Val Gly Lys Ala                 405 410 415 Met Tyr Ala Pro Pro Ile Lys Gly Pro Ile Lys Cys Ser Ser Asn Ile             420 425 430 Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Val Asn Asn Ser Glu Thr         435 440 445 Glu Thr Phe Arg Pro Gly Gly Gly Asp Met Arg Asn Asn Trp Arg Cys     450 455 460 Gly Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val Ala 465 470 475 480 Pro Thr Arg Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg                 485 490 <210> 85 <211> 1603 <212> DNA <213> Human immunodeficiency virus type 1 <400> 85 agaaagagca gagacagtgg caatgaaagt gaaggggatc aggaagaatt atcagcactt 60 gtggggatgg ggcatgatgc tccttgggat gttaatgatc tgtagtgcta cagaaaacct 120 gtgggtcaca gtatattgtg gggtacctgt gtggaaagaa gcagaaacca gtctattttg 180 tgcatcagat gctaacacat ataatacaga ggctcataat gtttgggcca ctcatgcctg 240 tgtacccacg gaccccaacc cacaagaaat atatttggaa aatgtgacag aaaattttaa 300 catgtggaaa aataacatgg tagaacagat gcatgaggat atagtaagtt tatgggatga 360 aagcctaaag ccatgtgtaa aaataacccc actctgtgtc actctaaatt gcactgattt 420 ggaaaatggc actagtagca ataatagtag ctatcaaagg ggggaagaag gagaaataaa 480 gaactgctct ttcaatatca ccacaagatt aagagaaaag gtacagaaag aatatgcact 540 tttttataaa cttgatataa tagcaatgga taataaaact aatgctacca gatataggtt 600 gataagttgt aacacctcaa ccattacaca ggcctgtcca aaagtatcct ttgagccaat 660 tcccatacat tattgtgccc cagctggttt tgcgcttttc aagtgtaatg ataagaagtt 720 caatggatca ggaacatgta acaatgtcag cacagtacaa tgtacacatg gaattaggcc 780 agtagtatca actcagctgt tgctaaatgg cagtctagca gaagaagagg tagtaattag 840 atctgaaaat ttcacaaaca gtgctaaaac cataatagta cagctaaaag aacctgtaaa 900 aattaattgt acaagaccca acaataatac aagaagaagt atacatatag gaccaggaaa 960 agcattttat gcaacaggag aaataatagg agatatagga caagcacatt gtaacattag 1020 tggacaagaa tggaataaaa ctttaattca gatagttaaa aaattgagag aacaatttgg 1080 gaataagacg ataaacttta ctaaaccagc aggaggggac ccagagattg taatgcacag 1140 ttttaattgt ggaggggaat ttttctactg tgatacaaca cgactgttta atagggcttg 1200 gaataatact gaagagttaa atagtactac tggagagtca aataacacta tcaccctccc 1260 atgcagaata aaacaaatta taaacatgtg gcaggaagta ggaaaagcaa tgtatgcccc 1320 tcccatccaa ggaacaatta gatgttcatc aaatattaca gggctgctac tagcaagaga 1380 tggtggcagt aacaatgaga ctaatactac tgaaatcttc agacctgcag gaggagatat 1440 gagggacaat tggagaagtg aattatataa atataaagta gtaaaaattg aaccattagg 1500 agtagcaccc accagggcaa agagaagagt ggtgcaaaga gaaagaagag caataggaat 1560 aggagctgtg ttccttgggt tcttgggagc agcaggaagc act 1603 <210> 86 <211> 482 <212> PRT <213> Human immunodeficiency virus type 1 <400> 86 Ser Ala Thr Glu Asn Leu Trp Val Thr Val Tyr Cys Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Glu Thr Ser Leu Phe Cys Ala Ser Asp Ala Asn Thr             20 25 30 Tyr Asn Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Ile Tyr Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Val Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys Val Lys Ile Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Leu Glu Asn Gly Thr Ser Ser             100 105 110 Asn Asn Ser Ser Tyr Gln Arg Gly Glu Glu Gly Glu Ile Lys Asn Cys         115 120 125 Ser Phe Asn Ile Thr Thr Arg Leu Arg Glu Lys Val Gln Lys Glu Tyr     130 135 140 Ala Leu Phe Tyr Lys Leu Asp Ile Ile Ala Met Asp Asn Lys Thr Asn 145 150 155 160 Ala Thr Arg Tyr Arg Leu Ile Ser Cys Asn Thr Ser Thr Ile Thr Gln                 165 170 175 Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala             180 185 190 Pro Ala Gly Phe Ala Leu Phe Lys Cys Asn Asp Lys Lys Phe Asn Gly         195 200 205 Ser Gly Thr Cys Asn Asn Val Ser Thr Val Gln Cys Thr His Gly Ile     210 215 220 Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu 225 230 235 240 Glu Glu Val Val Ile Arg Ser Glu Asn Phe Thr Asn Ser Ala Lys Thr                 245 250 255 Ile Ile Val Gln Leu Lys Glu Pro Val Lys Ile Asn Cys Thr Arg Pro             260 265 270 Asn Asn Asn Thr Arg Arg Ser Ile His Ile Gly Pro Gly Lys Ala Phe         275 280 285 Tyr Ala Thr Gly Glu Ile Ile Gly Asp Ile Gly Gln Ala His Cys Asn     290 295 300 Ile Ser Gly Gln Glu Trp Asn Lys Thr Leu Ile Gln Ile Val Lys Lys 305 310 315 320 Leu Arg Glu Gln Phe Gly Asn Lys Thr Ile Asn Phe Thr Lys Pro Ala                 325 330 335 Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys Gly Gly Glu             340 345 350 Phe Phe Tyr Cys Asp Thr Thr Arg Leu Phe Asn Arg Ala Trp Asn Asn         355 360 365 Thr Glu Glu Leu Asn Ser Thr Thr Gly Glu Ser Asn Asn Thr Ile Thr     370 375 380 Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly 385 390 395 400 Lys Ala Met Tyr Ala Pro Pro Ile Gln Gly Thr Ile Arg Cys Ser Ser                 405 410 415 Asn Ile Thr Gly Leu Leu Leu Ala Arg Asp Gly Gly Ser Asn Asn Glu             420 425 430 Thr Asn Thr Thr Glu Ile Phe Arg Pro Ala Gly Gly Asp Met Arg Asp         435 440 445 Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro     450 455 460 Leu Gly Val Ala Pro Thr Arg Ala Lys Arg Arg Val Val Gln Arg Glu 465 470 475 480 Arg Arg          <210> 87 <211> 1604 <212> DNA <213> Human immunodeficiency virus type 1 <400> 87 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tgtcagcact 60 tatggagatg gggcatcatg ctccttggaa tgttaatgat ctgtagtgct gcaagcctgt 120 gggtcacagt ctattatggg gtacctgtgt ggaaagatgc aaacaccact ctattttgtg 180 catcagatgc taaagcatat gatacagagg tacataatgt gtgggccaca catgcctgtg 240 tacccacaga ccccaaccca caagaagtag tattggaaaa tgtgacagaa aattttaata 300 tgtggaaaaa taacatggta gaacagatgc atgaggacat aattagttta tgggaccaaa 360 gcctaaagcc atgtgtaaaa ctaaccccac tctgtgttac tttaaattgc actgagttga 420 tgttgaatac tactaccaat agtactacta ccaatagtac cagtagtcct cctaccagta 480 gtggattgac aaactgctct ttcaatatcg ccacagatct aagagataag gtgcagaaag 540 aatatgctct tttttctaca cttgatgtag tatcaatagg taataacagc tctaggctga 600 taagttgtaa cacctcaatc cttacacagg cctgtccaaa ggtatccttt gagccaattc 660 ccatacatta ttgtgccccg gctggttttg caattctaaa gtgtaacaat aagacattca 720 atggaaaagg actatgtaac aatgtcagca caatacaatg tacacatgga attaagccag 780 tagtatcaac tcaattactg ttaaatggca gtctagcaga gaaagacata gtaattagat 840 ctgacaattt ttcaaacaat gctaagacca taatagtaca gctgaagaag cctgtataca 900 tcaattgtac aagacccaac aacaatacga gaaaaggtat acacatagca ccagggagag 960 cattttatac aacaggacag ataataggag acataaggaa agcatattgt gaaattagtg 1020 gaaaaagctg gaataacact ttagaacaga tagctacaaa attaagagaa caatttggga 1080 gtaataaaac aatagtcttt aatcaatcct cgggagggga cccagaaatt gtaatgcaca 1140 gttttaattg tagaggagaa tttttctatt gtaattcaac acaattgttt aatagtactt 1200 ggccgggtaa cggtcctagc aataatacta ctgggaatgg tactgatact gttatcatcc 1260 ttccatgcag aataaaacaa atcataaaca tgtggcagga agtaggaaga gcaatgtgtg 1320 cccctcccat cgcaggacaa attaactgta caacaaaaat tacagggctg ttattaacaa 1380 gagatggtgg gaatagcaat gagaccaaag agactgaaat ctttagacct ggaggaggag 1440 atatgaggga caattggaga agtgaattat acaaatataa agtagtaaaa attgaaccat 1500 taggagtagc acccaccgag gcaaggagaa gagtggtgca acgagaaaag agcagtggga 1560 ctaggagcta tgttccttgg gttcttggga gcagcagaag cact 1604 <210> 88 <211> 483 <212> PRT <213> Human immunodeficiency virus type 1 <400> 88 Ser Ala Ala Ser Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp 1 5 10 15 Lys Asp Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr             20 25 30 Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr         35 40 45 Asp Pro Asn Pro Gln Glu Val Val Leu Glu Asn Val Thr Glu Asn Phe     50 55 60 Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile Ile 65 70 75 80 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu                 85 90 95 Cys Val Thr Leu Asn Cys Thr Glu Leu Met Leu Asn Thr Thr Thr Asn             100 105 110 Ser Thr Thr Thr Asn Ser Thr Ser Ser Pro Pro Thr Ser Ser Gly Leu         115 120 125 Thr Asn Cys Ser Phe Asn Ile Ala Thr Asp Leu Arg Asp Lys Val Gln     130 135 140 Lys Glu Tyr Ala Leu Phe Ser Thr Leu Asp Val Val Ser Ile Gly Asn 145 150 155 160 Asn Ser Ser Arg Leu Ile Ser Cys Asn Thr Ser Ile Leu Thr Gln Ala                 165 170 175 Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro             180 185 190 Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Lys         195 200 205 Gly Leu Cys Asn Asn Val Ser Thr Ile Gln Cys Thr His Gly Ile Lys     210 215 220 Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Lys 225 230 235 240 Asp Ile Val Ile Arg Ser Asp Asn Phe Ser Asn Asn Ala Lys Thr Ile                 245 250 255 Ile Val Gln Leu Lys Lys Pro Val Tyr Ile Asn Cys Thr Arg Pro Asn             260 265 270 Asn Asn Thr Arg Lys Gly Ile His Ile Ala Pro Gly Arg Ala Phe Tyr         275 280 285 Thr Thr Gly Gln Ile Ile Gly Asp Ile Arg Lys Ala Tyr Cys Glu Ile     290 295 300 Ser Gly Lys Ser Trp Asn Asn Thr Leu Glu Gln Ile Ala Thr Lys Leu 305 310 315 320 Arg Glu Gln Phe Gly Ser Asn Lys Thr Ile Val Phe Asn Gln Ser Ser                 325 330 335 Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys Arg Gly Glu             340 345 350 Phe Phe Tyr Cys Asn Ser Thr Gln Leu Phe Asn Ser Thr Trp Pro Gly         355 360 365 Asn Gly Pro Ser Asn Asn Thr Thr Gly Asn Gly Thr Asp Thr Val Ile     370 375 380 Ile Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val 385 390 395 400 Gly Arg Ala Met Cys Ala Pro Pro Ile Ala Gly Gln Ile Asn Cys Thr                 405 410 415 Thr Lys Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Ser Asn             420 425 430 Glu Thr Lys Glu Thr Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg         435 440 445 Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu     450 455 460 Pro Leu Gly Val Ala Pro Thr Glu Ala Arg Arg Arg Val Val Gln Arg 465 470 475 480 Glu lys ser              <210> 89 <211> 1666 <212> DNA <213> Human immunodeficiency virus type 1 <400> 89 agaaagagca gagacagtgg caatgagagc gaaggagacc aggaagaatt gtcagcactc 60 gtggggatgg ggaaccatgc tcctgtggag atggggcatc atgctccttg ggatgttaat 120 gatctgtagt gctaaagaaa atttgtgggt cacagtctat tatggggtac ctgtgtggaa 180 agaagcatcc accactctat tttgtgcatc agatgctaaa gcatatgata cagaggtaca 240 taatgtttgg gccacacatg cctgtgtacc cacagacccc agcccacaag aagtagtatt 300 gggaaatgtg acagaatgtt ttaacatgtg gaataacaac atggtagaac agatgcatga 360 ggatataatc agtttatggg accaaagtct aaaaccctgt gtaaaattaa ccccactctg 420 tgttacctta agttgcagtg acgttaatat taccaatatt atcaataaca ctattgctaa 480 aaataatagt ttaagaatgg aaacaggaga cataaaaaac tgctctttca atatcaccac 540 aaacataaga gataagatgc aaacagaata tgcacttttt tataaatttg atgtagtgcc 600 aatatatgat agcaatgatg atagcaatat tactagaaat gatagttata ggataataag 660 ttgtaatacc tcagtcatta cacaggcctg tccaaaggta acctttgagc caattcccat 720 acattattgt gccccggctg gttttgcgat tctaaagtgt aacaataaga cattcaatgg 780 aaaaggacca tgtacaaatg tcagcacagt acaatgtaca catggaatta ggccagtagt 840 gtcaactcaa ctactgttaa atggcagtct agcagaaaag gagatagtga ttagatctga 900 caatttctcg gacaatgcta aaactataat agtacagtta aatggaactg ttcaaattaa 960 ttgttcaaga cccggcaaca atacaagaaa aagtatacat ataggaccag ggagtgcatt 1020 ttatgcaaca ggagacataa taggagatat aagaaaagca cattgtaaca ttagtaaaac 1080 agactggaat aacactttag gaaagatagc aaaaaaatta agagaacaat ttggggaaaa 1140 taaaacaata gagtttgaga aatccacagg aggggaccca gaagttatga tgcatacttt 1200 taattgtgga ggggaatttt tctactgtaa ttcaacaccg ctgtttaatg gtagtacttt 1260 taataatact tggacacctt tgaatagtag tgctaaaggg ccaaatgaca ctctcatact 1320 ccaatgtaga ataaaacaaa tcataaacat gtggcaggaa gtaggaaaag caatgtatgc 1380 ccctcccatc agaggataca ttaattgttc atcaaatatt acagggctgc tattgacaag 1440 agatggtggt aataatactg gtaatgatag caataccgag accttcagac ctacaggagg 1500 aaatatgaag gacaattgga ggagtgaatt atataaatat aaagtagtac aaattgaacc 1560 attaggagta gcacccacca gggcaaaaag aagagtggtg cagagagaaa aaagagcagc 1620 gctgggggct atgttccttg ggttcttggg agcagcagga agcact 1666 <210> 90 <211> 496 <212> PRT <213> Human immunodeficiency virus type 1 <400> 90 Ser Ala Lys Glu Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Ser Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Ser Pro Gln Glu Val Val Leu Gly Asn Val Thr Glu Cys     50 55 60 Phe Asn Met Trp Asn Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Ser Cys Ser Asp Val Asn Ile Thr Asn Ile Ile             100 105 110 Asn Asn Thr Ile Ala Lys Asn Asn Ser Leu Arg Met Glu Thr Gly Asp         115 120 125 Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Asn Ile Arg Asp Lys Met     130 135 140 Gln Thr Glu Tyr Ala Leu Phe Tyr Lys Phe Asp Val Val Pro Ile Tyr 145 150 155 160 Asp Ser Asn Asp Asp Ser Asn Ile Thr Arg Asn Asp Ser Tyr Arg Ile                 165 170 175 Ile Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Thr             180 185 190 Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile         195 200 205 Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Lys Gly Pro Cys Thr Asn     210 215 220 Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr 225 230 235 240 Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Lys Glu Ile Val Ile Arg                 245 250 255 Ser Asp Asn Phe Ser Asp Asn Ala Lys Thr Ile Ile Val Gln Leu Asn             260 265 270 Gly Thr Val Gln Ile Asn Cys Ser Arg Pro Gly Asn Asn Thr Arg Lys         275 280 285 Ser Ile His Ile Gly Pro Gly Ser Ala Phe Tyr Ala Thr Gly Asp Ile     290 295 300 Ile Gly Asp Ile Arg Lys Ala His Cys Asn Ile Ser Lys Thr Asp Trp 305 310 315 320 Asn Asn Thr Leu Gly Lys Ile Ala Lys Lys Leu Arg Glu Gln Phe Gly                 325 330 335 Glu Asn Lys Thr Ile Glu Phe Glu Lys Ser Thr Gly Gly Asp Pro Glu             340 345 350 Val Met Met His Thr Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn         355 360 365 Ser Thr Pro Leu Phe Asn Gly Ser Thr Phe Asn Asn Thr Trp Thr Pro     370 375 380 Leu Asn Ser Ser Ala Lys Gly Pro Asn Asp Thr Leu Ile Leu Gln Cys 385 390 395 400 Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met                 405 410 415 Tyr Ala Pro Pro Ile Arg Gly Tyr Ile Asn Cys Ser Ser Asn Ile Thr             420 425 430 Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Asn Thr Gly Asn Asp Ser         435 440 445 Asn Thr Glu Thr Phe Arg Pro Thr Gly Gly Asn Met Lys Asp Asn Trp     450 455 460 Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Gln Ile Glu Pro Leu Gly 465 470 475 480 Val Ala Pro Thr Arg Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg                 485 490 495 <210> 91 <211> 1559 <212> DNA <213> Human immunodeficiency virus type 1 <400> 91 agaaagagca gaagacagtg gcaatgagag tgaaggagat caggaagaac tatcagcact 60 tgtggagatg gggcatcatg ctctttggga tattaatgat ctgtagtgct gaagaaaagt 120 gggtcacagt ctattatggg gtacctgtgt ggaaagaagc aaagaccact ctattttgtg 180 catcagatgc taaagcatat gatacagagg cacataatgt ttgggccaca catgcctgtg 240 tacccacaga ccccaaccca caagaagtag tattggagaa tgtgacagaa aattttaaca 300 tgtggaaaaa tgacatggta gagcagatgc atgaggatgt aatcagttta tgggatcaaa 360 gcctaaagcc atgtgtagaa ttaacgccac tctgtgttac tctaaattgc actaatctaa 420 attgcactaa caacactagt agcgaaataa aaaactgttc tttctatgtc accacaagca 480 tggaaggtaa ggtgaaaaaa catgcaacgt tttatagcct tgatatagta cgaacaacag 540 agagtaatat cagctatagg ttgataagtt gtaacacctc agtcattaca caggcctgtc 600 caaaaatatc ctttgaacca attcccatac attattgtgc cccggctggt tttgcgatcc 660 taaagtgtaa caataagaca ttcaatggaa caggaccatg tacaaatgtc agcacagtgc 720 aatgtacaca tggaattaag ccagtagtat caactcaact actgttaaat ggcagtctag 780 cagaggaaga ggtagtaatt agatctgaaa atttcatgag aaatgataaa atcataatag 840 tacagctaaa tgaatctata gaaattaatt gtacaagacc caactataat acaagaaaag 900 gtttccatat aggaccaggg agagcaattt atacaggaca aataatagga gatatcagac 960 aagcacattg taacattagt ggaataaaat ggaagaaggc tttaaaacag atagttggaa 1020 aattaagaga acaatttggg aataaaacaa tagtatttaa tcagtcctca ggaggggacc 1080 tagaaattga aacacacagt tttaattgtg gaggggaatt tttctactgc aatacaacac 1140 aactgtttaa taatacttgg ccgtcaaata atactgacgg agatattaac gaaaacatca 1200 cactcacact cccatgcaga ataaaacaaa ttataaacat gtggcagaaa gtaggaaaag 1260 ccatgtatgc ccctcccatc aaaggacaaa ttagatgttc atcaaatatt acagggctgc 1320 tactaatgag agatggtggt aacgacacca ccaaggcaaa cgacaccgag gtcttcagac 1380 ctggaggagg ggagatgagg gacaattgga gaagtgaatt atataaatat aaagtagtaa 1440 aaattgaacc attaggaata gcacccacca aggcaaagag aagagtggtg cagagagaaa 1500 aaagaggagt aggattagga gctatgttcc ttgggttctt gggagcagca ggaagcact 1559 <210> 92 <211> 467 <212> PRT <213> Human immunodeficiency virus type 1 <400> 92 Ser Ala Glu Glu Lys Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp 1 5 10 15 Lys Glu Ala Lys Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr             20 25 30 Asp Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr         35 40 45 Asp Pro Asn Pro Gln Glu Val Val Leu Glu Asn Val Thr Glu Asn Phe     50 55 60 Asn Met Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Val Ile 65 70 75 80 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Glu Leu Thr Pro Leu                 85 90 95 Cys Val Thr Leu Asn Cys Thr Asn Leu Asn Cys Thr Asn Asn Thr Ser             100 105 110 Ser Glu Ile Lys Asn Cys Ser Phe Tyr Val Thr Thr Ser Met Glu Gly         115 120 125 Lys Val Lys Lys His Ala Thr Phe Tyr Ser Leu Asp Ile Val Arg Thr     130 135 140 Thr Glu Ser Asn Ile Ser Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val 145 150 155 160 Ile Thr Gln Ala Cys Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile His                 165 170 175 Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr             180 185 190 Phe Asn Gly Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr         195 200 205 His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser     210 215 220 Leu Ala Glu Glu Glu Val Val Ile Arg Ser Glu Asn Phe Met Arg Asn 225 230 235 240 Asp Lys Ile Ile Ile Val Gln Leu Asn Glu Ser Ile Glu Ile Asn Cys                 245 250 255 Thr Arg Pro Asn Tyr Asn Thr Arg Lys Gly Phe His Ile Gly Pro Gly             260 265 270 Arg Ala Ile Tyr Thr Gly Gln Ile Ile Gly Asp Ile Arg Gln Ala His         275 280 285 Cys Asn Ile Ser Gly Ile Lys Trp Lys Lys Ala Leu Lys Gln Ile Val     290 295 300 Gly Lys Leu Arg Glu Gln Phe Gly Asn Lys Thr Ile Val Phe Asn Gln 305 310 315 320 Ser Ser Gly Gly Asp Leu Glu Ile Glu Thr His Ser Phe Asn Cys Gly                 325 330 335 Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn Asn Thr Trp             340 345 350 Pro Ser Asn Asn Thr Asp Gly Asp Ile Asn Glu Asn Ile Thr Leu Thr         355 360 365 Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Lys Val Gly     370 375 380 Lys Ala Met Tyr Ala Pro Pro Ile Lys Gly Gln Ile Arg Cys Ser Ser 385 390 395 400 Asn Ile Thr Gly Leu Leu Leu Met Arg Asp Gly Gly Asn Asp Thr Thr                 405 410 415 Lys Ala Asn Asp Thr Glu Val Phe Arg Pro Gly Gly Gly Glu Met Arg             420 425 430 Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu         435 440 445 Pro Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg     450 455 460 Glu lys arg 465 <210> 93 <211> 1691 <212> DNA <213> Human immunodeficiency virus type 1 <400> 93 agaaagagca gaagacagtg gcaatgagag tgaaggagat caagaggagt tatcagctct 60 tgttgaaagg gggcatcttg ctccttggga tattgatgat ctgtagtgct acagacaact 120 tgtgggtcac agtatattat ggggtacctg tatggaaaga agcaaccacc actctatttt 180 gtgcatcaga tgctaaagcc cataatacag aggtacacaa tgtttgggcc acacatgcct 240 gtgtacccac agaccctgac ccacaagaag tagtattgga aaatgtgaca gaaaatttta 300 acatgtggaa aaatgacatg gtagaacaga tgcatgagga tataatcagt ttatgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cactttgtgt tactttaaat tgcactaatg 420 ctaaaatgaa caatactgct gataccaatg ctactaatac tgttaatatc agcaaggaag 480 aaatggaaga aataaaaaac tgctctttca atgtcaccac aagcttaaga gataagatgc 540 agagccaata tgcattgttt tataaacttg atatagtacc aatagataat agtagtagta 600 tagataatag tagtaataca tgtaatagta atagtacaca taataatagt agtacatgta 660 ataattatgc taattataga ttgataagtt gtgacacctc agtcattaca caggcctgtc 720 caaaggtatc ctttgagcca attcccatac attattgtgc cccggctggt tttgcgattc 780 taaagtgtaa taataagacg ttcaatggat caggaccatg taaaaatgtc agcacagtac 840 aatgtacaca tggaatcagg ccagtagtat caactcaact gctgttaaat ggcagtctag 900 cagaagaagg ggtagttatt agatctgaga atttcacaaa caatgctaaa accataatag 960 tacagataca tgaacctata gaaattaatt gtacaagacc caacaacaat acaagaaaaa 1020 gtataactat aggaccagga agagcgtttt atgcaacagg agacataata ggagatataa 1080 gacaagcaca ttgtaacctt agtaaagcaa gatggaatga tactttaaaa cagatagtta 1140 caaaattaag agaacagttt agaaataaaa caataaattt tactcaatcc tcaggagggg 1200 acccagaaat tgtgatgcac agttttaatt gtggagggga atttttctac tgtaatacaa 1260 cacaactgtt taatagtact tggttgtcta atagtacttg gaatgatact gaaaggtcaa 1320 atggcactga aactattaca ctcccatgca gaataaagca agttataaac aggtggcagg 1380 aagtaggaaa agcaatgtat gcccctccca tcagtggaat aattagatgt tcatcaaata 1440 ttacagggct gctattaaca agagatggtg gtaatagtaa tgacactccg actgatactg 1500 agatcttcag acctggagga ggagatatga gggacaattg gagaagcgaa ttatataaat 1560 ataaagtagt aaaaattgaa ccattaggaa tagcacccac caaggcaaag agaagagtgg 1620 tgcagagaga aaaaagagca gcgggaatag gagctctgtt ccttgggttc ttgggagcag 1680 caggaagcac t 1691 <210> 94 <211> 511 <212> PRT <213> Human immunodeficiency virus type 1 <400> 94 Ser Ala Thr Asp Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 His Asn Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asp Pro Gln Glu Val Val Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asn Ala Lys Met Asn Asn Thr Ala             100 105 110 Asp Thr Asn Ala Thr Asn Thr Val Asn Ile Ser Lys Glu Glu Met Glu         115 120 125 Glu Ile Lys Asn Cys Ser Phe Asn Val Thr Thr Ser Leu Arg Asp Lys     130 135 140 Met Gln Ser Gln Tyr Ala Leu Phe Tyr Lys Leu Asp Ile Val Pro Ile 145 150 155 160 Asp Asn Ser Ser Ser Ile Asp Asn Ser Ser Asn Thr Cys Asn Ser Asn                 165 170 175 Ser Thr His Asn Asn Ser Ser Thr Cys Asn Asn Tyr Ala Asn Tyr Arg             180 185 190 Leu Ile Ser Cys Asp Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val         195 200 205 Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala     210 215 220 Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Ser Gly Pro Cys Lys 225 230 235 240 Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser                 245 250 255 Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Gly Val Val Ile             260 265 270 Arg Ser Glu Asn Phe Thr Asn Asn Ala Lys Thr Ile Ile Val Gln Ile         275 280 285 His Glu Pro Ile Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg     290 295 300 Lys Ser Ile Thr Ile Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly Asp 305 310 315 320 Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn Leu Ser Lys Ala Arg                 325 330 335 Trp Asn Asp Thr Leu Lys Gln Ile Val Thr Lys Leu Arg Glu Gln Phe             340 345 350 Arg Asn Lys Thr Ile Asn Phe Thr Gln Ser Ser Gly Gly Asp Pro Glu         355 360 365 Ile Val Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn     370 375 380 Thr Thr Gln Leu Phe Asn Ser Thr Trp Leu Ser Asn Ser Thr Trp Asn 385 390 395 400 Asp Thr Glu Arg Ser Asn Gly Thr Glu Thr Ile Thr Leu Pro Cys Arg                 405 410 415 Ile Lys Gln Val Ile Asn Arg Trp Gln Glu Val Gly Lys Ala Met Tyr             420 425 430 Ala Pro Pro Ile Ser Gly Ile Ile Arg Cys Ser Ser Asn Ile Thr Gly         435 440 445 Leu Leu Leu Thr Arg Asp Gly Gly Asn Ser Asn Asp Thr Pro Thr Asp     450 455 460 Thr Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg 465 470 475 480 Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Ile                 485 490 495 Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg             500 505 510 <210> 95 <211> 1616 <212> DNA <213> Human immunodeficiency virus type 1 <400> 95 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tgtcagcgct 60 ggtggagatg gggcatcatg ctccttggga tgttgatgat ctgtaaagct gcagaccaat 120 tgtgggtcac agtctattat ggggtacctg tgtggaagga agcaaccacc actttatttt 180 gtgcatcaga tgctaaagca tataagacag aggtacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaat ccacaagaaa tagacttggc aaatgtgaca gaaaatttta 300 acatgtggaa aaataacatg gtagaacaga tgcatgagga tataatcagt ttatgggatc 360 aaagcctaaa gccatgtgta aaactaaccc cactctgtgt tactttaaat tgtactgatg 420 acttagaaaa ttgtaaaaat accactaata ataatgccgc taataataat aatacctgcg 480 acatgccagg agaaataaag aactgctctt tcaatatcac cgcaggtata agagataaga 540 tgcagaaaga atatgcactt tttaatacac ttgatgtagt accaataggt gatgagaatg 600 ataataccag ttataggtta ataagttgta atacctcagt cattacacag gcctgtccaa 660 aggtatcctt tgagccaatt cccatacatt attgtgcccc ggctggtttt gcgattctaa 720 agtgtaaaga taagaaattc aatgggacag gacagtgtaa aaatgtcagc acagtacaat 780 gtacacatgg aattaagcca gtagtatcaa ctcaattact gttaaatggc agtctagcag 840 aagaagaggt agtaattagg tctgaaaatt tcacaaacaa tgctaaaacc ataatagtac 900 agctgaaaga acctgtacaa attaattgta caaggcccaa caacaataca agaaaaagca 960 tacatatagg accagggaga gcattttatg caacaggaca aataatagga gatataagac 1020 aagcacattg taacattagt agtataaaat ggaataacac tttaaaacag atagttaaaa 1080 aattaagaga acaatttaat aaaacaataa tctttaatca atcctcagga ggggacccag 1140 aaattgtaat gcacattttt aattgtagag gggaattttt ctactgtaat acaacacaac 1200 tgtttaatag cacttggaat attactgaag ggtcaaatga caatattaca ggcaggtcaa 1260 atgacactat cacgctccca tgcaagataa gacaaattgt aaacatgtgg caggaagtag 1320 gaaaagcaat gtatgctcct cccatcagag gacaaattaa ctgtacatca aatattacag 1380 ggctgctgtt aacaagagat ggtggtaaaa atatcagcga gtccgaaacc ttcagacctg 1440 gaggaggaaa tatgaaggac aattggagaa gtgaattata taaatacaaa gtagtacaaa 1500 ttgaaccatt aggagtagca cccaccaagg caaagagaag agtggtgcag agagaaaaaa 1560 gagcagtggg aataggagct ctgttccttg ggttcttggg agcagcagga agcact 1616 <210> 96 <211> 486 <212> PRT <213> Human immunodeficiency virus type 1 <400> 96 Lys Ala Ala Asp Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Lys Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Ile Asp Leu Ala Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Asp Leu Glu Asn Cys Lys Asn             100 105 110 Thr Thr Asn Asn Asn Ala Ala Asn Asn Asn Asn Thr Cys Asp Met Pro         115 120 125 Gly Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr Ala Gly Ile Arg Asp     130 135 140 Lys Met Gln Lys Glu Tyr Ala Leu Phe Asn Thr Leu Asp Val Val Pro 145 150 155 160 Ile Gly Asp Glu Asn Asp Asn Thr Ser Tyr Arg Leu Ile Ser Cys Asn                 165 170 175 Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile             180 185 190 Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Lys         195 200 205 Asp Lys Lys Phe Asn Gly Thr Gly Gln Cys Lys Asn Val Ser Thr Val     210 215 220 Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu 225 230 235 240 Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser Glu Asn Phe                 245 250 255 Thr Asn Asn Ala Lys Thr Ile Ile Val Gln Leu Lys Glu Pro Val Gln             260 265 270 Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile His Ile         275 280 285 Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly Gln Ile Ile Gly Asp Ile     290 295 300 Arg Gln Ala His Cys Asn Ile Ser Ser Ile Lys Trp Asn Asn Thr Leu 305 310 315 320 Lys Gln Ile Val Lys Lys Leu Arg Glu Gln Phe Asn Lys Thr Ile Ile                 325 330 335 Phe Asn Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ile Phe             340 345 350 Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn         355 360 365 Ser Thr Trp Asn Ile Thr Glu Gly Ser Asn Asp Asn Ile Thr Gly Arg     370 375 380 Ser Asn Asp Thr Ile Thr Leu Pro Cys Lys Ile Arg Gln Ile Val Asn 385 390 395 400 Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly                 405 410 415 Gln Ile Asn Cys Thr Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp             420 425 430 Gly Gly Lys Asn Ile Ser Glu Ser Glu Thr Phe Arg Pro Gly Gly Gly         435 440 445 Asn Met Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val     450 455 460 Gln Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val 465 470 475 480 Val Gln Arg Glu Lys Arg                 485 <210> 97 <211> 1640 <212> DNA <213> Human immunodeficiency virus type 1 <400> 97 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tatcagcact 60 ggtggagatg ggggaccatg ctcctttggt tattgatgat ctgtagtgct gcagaacaat 120 tgtgggtcac agtttactat ggggtacctg tgtggaaaga agcaaccacc actctatttt 180 gtgcatcaga tgccaaagca tatgatccag aggcacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaat tagtattggc aaatgtgaca gaaaatttta 300 acatgtggaa aaataacatg gtagaacaga tgcaggagga tataatcagt ttatgggatc 360 aaagcctaaa gccatgtaca aaattaaccc cactctgtgt tactttaaat tgtactgatg 420 tggagtataa taatgaaact gcttccaata atactgcttc caatactact attattaatg 480 ggggaacaat agagggagat ggaataaaaa actgctcttt caatatcacc accagcctaa 540 ataaggtgca gaaagaaaat gcatattttt ataatcttga tgtagtacaa atagataata 600 gtgataatac cagctatagg ttagtaagtt gtaacacctc agtcattaca caggcctgtc 660 caaagatatc ttttgagcca attcccatac attactgtac cccggctggt tttgcgattc 720 taaagtgtaa tgataaaaag ttcaatggaa caggaccatg taaaaatgtc agcacagtac 780 aatgtacaca tggaattaag ccagtagtat caactcaact gttgttaaat ggcagtctag 840 cagaagaaga ggtagtaatt agatcagaaa atttcacaga taatgcaaaa atcataatag 900 tacagctgaa tgaatctatg gaaattaatt gtgcaagacc caacaacaat acaagaaaag 960 gtatacatat gggaccaggg aaagcatttt atgcaacagg agccataata ggagatatac 1020 gaagagcaca ttgcaacatt agtcaaacaa agtggaacaa tgccctaaaa cagatagcta 1080 taaagttaag agaacaattt gggaataaaa caatagtctt tacaaactcc tcaggagggg 1140 acccagaaat tgtaatgcac agttttaact gtggagggga gtttttctac tgtaatacat 1200 cactcctgtt taatagtatc tggaatagta ctactttgtc aaatagcact acaggagatg 1260 gaaatatcac actcccatgc agaataaaac aaattataaa tatgtggcag aaagtaggga 1320 aagcaatgta tgcccctccc atccaaggac taattaaatg tacatcaaat atcacaggga 1380 tgttattaat aagagatggt ggtaacatca actgcactga gactaatacc accaactgca 1440 atgagactga gaccttcaga cctgtaggag gagatatgag ggacaattgg agaagtgaat 1500 tatataaata taaagtagta aaaattgaac cattaggaat agcacccact aaggcaaaga 1560 gaagagtggt gcagagagaa aaaagagcag cgggactagg agctttgttc cttgggttct 1620 tgggagcagc aggaagcact 1640 <210> 98 <211> 494 <212> PRT <213> Human immunodeficiency virus type 1 <400> 98 Ser Ala Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Pro Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Leu Val Leu Ala Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met Gln Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Thr Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Val Glu Tyr Asn Asn Glu Thr             100 105 110 Ala Ser Asn Asn Thr Ala Ser Asn Thr Thr Ile Ile Asn Gly Gly Thr         115 120 125 Ile Glu Gly Asp Gly Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Ser     130 135 140 Leu Asn Lys Val Gln Lys Glu Asn Ala Tyr Phe Tyr Asn Leu Asp Val 145 150 155 160 Val Gln Ile Asp Asn Ser Asp Asn Thr Ser Tyr Arg Leu Val Ser Cys                 165 170 175 Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Ile Ser Phe Glu Pro             180 185 190 Ile Pro Ile His Tyr Cys Thr Pro Ala Gly Phe Ala Ile Leu Lys Cys         195 200 205 Asn Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr     210 215 220 Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu 225 230 235 240 Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser Glu Asn                 245 250 255 Phe Thr Asp Asn Ala Lys Ile Ile Ile Val Gln Leu Asn Glu Ser Met             260 265 270 Glu Ile Asn Cys Ala Arg Pro Asn Asn Asn Thr Arg Lys Gly Ile His         275 280 285 Met Gly Pro Gly Lys Ala Phe Tyr Ala Thr Gly Ala Ile Gly Asp     290 295 300 Ile Arg Arg Ala His Cys Asn Ile Ser Gln Thr Lys Trp Asn Asn Ala 305 310 315 320 Leu Lys Gln Ile Ala Ile Lys Leu Arg Glu Gln Phe Gly Asn Lys Thr                 325 330 335 Ile Val Phe Thr Asn Ser Ser Gly Gly Asp Pro Glu Ile Val Met His             340 345 350 Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Leu Leu         355 360 365 Phe Asn Ser Ile Trp Asn Ser Thr Thr Leu Ser Asn Ser Thr Thr Gly     370 375 380 Asp Gly Asn Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met 385 390 395 400 Trp Gln Lys Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Gln Gly Leu                 405 410 415 Ile Lys Cys Thr Ser Asn Ile Thr Gly Met Leu Leu Ile Arg Asp Gly             420 425 430 Gly Asn Ile Asn Cys Thr Glu Thr Asn Thr Thr Asn Cys Asn Glu Thr         435 440 445 Glu Thr Phe Arg Pro Val Gly Gly Asp Met Arg Asp Asn Trp Arg Ser     450 455 460 Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Ile Ala 465 470 475 480 Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg                 485 490 <210> 99 <211> 1649 <212> DNA <213> Human immunodeficiency virus type 1 <400> 99 agaaagagca gaagacagtg gcaatgagag tgaaggagat caggaggaat tgtcagcact 60 ggtggtggaa atggggcacc atgctccttg ggatgttgat gatctgtagt gctaacgagc 120 aattgtgggt cacagtctat tatggggtac ctgtgtggaa agaagcaacc accactctat 180 tttgtgcatc agatgctaaa gcatatgaca cagaggcaca taatgtttgg gccacacatg 240 cctgtgtacc cacagaccct aacccacaag aagtagtatt ggtaaatgtg acagaaaatt 300 ttaatatgtg gaaaaataac atggtagaac agacgcagga ggatataatc agtttatggg 360 atcaaagcct aaagccatgt gtaaaattaa ccccactctg tgttactcta aattgcactg 420 attggaccct acattgcaat aataatgata ctaattgcac tactttaaaa aatgatacta 480 aaaccaataa taatagtagt ttgagaacaa tggagggagg agaagtaaaa aactgctctt 540 tcaatgtcac cacaagccta agagataagg agcgaaaaga atatgcactt ttttataaac 600 ttgatgtagt accaataggt aatgataata caagctatac gctgataaat tgtaacacct 660 caaccattac acaggcctgt ccaaaggtaa cctttgaacc aattcccata cattattgta 720 ccccggctgg ttttgcgctt ctaaagtgta atgataagaa gttcaatgga acaggacagt 780 gtaaaaatgt cagcacagta caatgtacac atggaattag gccagtagta tcaactcaat 840 tgctgctaaa tggcagtcta tcagaaggag aggtaatgat tagatctgaa aatttcacaa 900 acaatgctaa aaccataata gtacagctga atgaatctat agcaattaat tgtacaagac 960 ccaacaacaa tacaagaaaa agtataacta taggaccggg gagagcattt tttacaacag 1020 gagaaataac aggagatata agacaagcac attgtaacct tagtgcagta caatggaata 1080 acacattaaa acagatagtt gcaaaattaa gggaacaatt tgggaataat acaataagct 1140 ttaataaatc cgcaggaggg gacccagaaa ttgtaatgca cagttttaat tgtggagggg 1200 aatttttcta ctgtgataca acacagctgt ttaatagtac ttgggataat gacacagact 1260 taagtattaa gaatgagact acagaatcaa acaacaaaac tatcacactc ccgtgcagaa 1320 taaaacaaat tataaacaga tggcaggaag taggaaaagc aatgtatgcc cctcccatca 1380 gaggacaaat taaatgttca tcaaatatta cagggctact attaacaaga gatggtggta 1440 tgaacaatag cgccaacgag accttcagac ctggaggagg agatatgagg gacaattgga 1500 gaagtgaatt atataaatat aaagtagtaa aaattgagcc attaggggta gcacccacca 1560 aggcaaagag aagagcggtg caaagagaaa aaagagcagt gggaatagga gctgtgttcc 1620 ttgggttctt gggagcagca ggaagcact 1649 <210> 100 <211> 496 <212> PRT <213> Human immunodeficiency virus type 1 <400> 100 Ser Ala Asn Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Val Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Thr Gln Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Trp Thr Leu His Cys Asn Asn             100 105 110 Asn Asp Thr Asn Cys Thr Thr Leu Lys Asn Asp Thr Lys Thr Asn Asn         115 120 125 Asn Ser Ser Leu Arg Thr Met Glu Gly Gly Glu Val Lys Asn Cys Ser     130 135 140 Phe Asn Val Thr Thr Ser Ser Leu Arg Asp Lys Glu Arg Lys Glu Tyr Ala 145 150 155 160 Leu Phe Tyr Lys Leu Asp Val Val Pro Ile Gly Asn Asp Asn Thr Ser                 165 170 175 Tyr Thr Leu Ile Asn Cys Asn Thr Ser Thr Ile Thr Gln Ala Cys Pro             180 185 190 Lys Val Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Thr Pro Ala Gly         195 200 205 Phe Ala Leu Leu Lys Cys Asn Asp Lys Lys Phe Asn Gly Thr Gly Gln     210 215 220 Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val 225 230 235 240 Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ser Glu Gly Glu Val                 245 250 255 Met Ile Arg Ser Glu Asn Phe Thr Asn Asn Ala Lys Thr Ile Ile Val             260 265 270 Gln Leu Asn Glu Ser Ile Ala Ile Asn Cys Thr Arg Pro Asn Asn Asn         275 280 285 Thr Arg Lys Ser Ile Thr Ile Gly Pro Gly Arg Ala Phe Phe Thr Thr     290 295 300 Gly Glu Ile Thr Gly Asp Ile Arg Gln Ala His Cys Asn Leu Ser Ala 305 310 315 320 Val Gln Trp Asn Asn Thr Leu Lys Gln Ile Val Ala Lys Leu Arg Glu                 325 330 335 Gln Phe Gly Asn Asn Thr Ile Ser Phe Asn Lys Ser Ala Gly Gly Asp             340 345 350 Pro Glu Ile Val Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr         355 360 365 Cys Asp Thr Thr Gln Leu Phe Asn Ser Thr Trp Asp Asn Asp Thr Asp     370 375 380 Leu Ser Ile Lys Asn Glu Thr Thr Glu Ser Asn Asn Lys Thr Ile Thr 385 390 395 400 Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Arg Trp Gln Glu Val Gly                 405 410 415 Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Gln Ile Lys Cys Ser Ser             420 425 430 Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Met Asn Asn Ser         435 440 445 Ala Asn Glu Thr Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp     450 455 460 Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly 465 470 475 480 Val Ala Pro Thr Lys Ala Lys Arg Arg Ala Val Gln Arg Glu Lys Arg                 485 490 495 <210> 101 <211> 1610 <212> DNA <213> Human immunodeficiency virus type 1 <400> 101 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tgcttacgga 60 aatggggcac catgctcctt gggatattaa tgatctgtag tgctgcagga aatttgtggg 120 tcacagtcta ttatggggtg cctgtgtgga aagaagcaac caccactcta ttctgtgcat 180 cagatgctaa agcatatgct acagaggcac ataatgtttg ggccacacat gcctgtgtac 240 ccacagaccc taacccacaa gaagtagtaa tggaaaatgt gacagaaaat tttaacatgt 300 ggaaaaataa catggtagaa cagatgcatg aggatataat cagtttatgg gatcaaagcc 360 taaagccatg tgtaaaatta accccactct gtgttactct aaattgcact gactgtgtga 420 cttcaaattg cactaagttg aagaatgtca ctaataatgc taatattagc aagatggaga 480 tggaggaggg agaaatgaaa aactgctctt ttaacatcac ctcaggcatg agagataaga 540 tgaagaaaga atatgcattt ttttataaac ttgatatagt accaataagt aatgataata 600 ctagctatag attgataagt tgtaatacct cagtcattac acaggcatgt ccaaaagtat 660 cctttgagcc aattcccata cattattgtg ccccggctgg ttttgcgatt ctaaaatgta 720 atgataagaa gttcaatgga acaggaccat gtaaaaatgt cagcacagta caatgtacac 780 atggaattag gccagtagtg tcaactcaat tgctgttaaa tggcagccta gcagaagaag 840 aggtagtaat tagatctgaa aatttaacgg acaatggtaa aaccataata gtacagctga 900 acgaatctgt acacattaat tgtacaagac ccagcaacaa taccagaaaa agtatacata 960 taggaccagg gaaagcattt tatgcaacag gacaaataat aggagatata agacaagcac 1020 actgtaacat tagtgaaaaa caatggaata aaactttaag ccagatagtt aaaaaattaa 1080 gagaacaatt taaaaataaa acaatagtct ttaatcaatc ctcaggaggg gacccagaaa 1140 ttgtaatgca cagttttaat tgtggaggag aatttttcta ctgtaattca acacaactat 1200 ttaatactac ttggaattgg aatgatactg aagggtcaaa taacactgaa agaaatgaaa 1260 gaaatattac actcccatgc agaataaaac aaattgtaaa caggtggcag gaagtaggaa 1320 aagcaatgta tgcccctccc atcagcggac caattagctg ttcatcaaat attacagggc 1380 tgctattaac aagagatggt ggtctcccaa acaatactga gaccttcaga ccagaaggag 1440 gaaatatgaa ggacaattgg agaagtgaat tatataaata taaagtagta aaaattgaac 1500 cattaggaat agcacccacc aaggcaaaga gaagagtggt gcaaagagaa aaaagagcag 1560 tgacattagg agctatgttc cttgggttct tgggagcagc aggaagcact 1610 <210> 102 <211> 486 <212> PRT <213> Human immunodeficiency virus type 1 <400> 102 Ser Ala Ala Gly Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Ala Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Met Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Cys Val Thr Ser Asn Cys Thr             100 105 110 Lys Leu Lys Asn Val Thr Asn Asn Ala Asn Ile Ser Lys Met Glu Met         115 120 125 Glu Glu Gly Glu Met Lys Asn Cys Ser Phe Asn Ile Thr Ser Gly Met     130 135 140 Arg Asp Lys Met Lys Lys Glu Tyr Ala Phe Phe Tyr Lys Leu Asp Ile 145 150 155 160 Val Pro Ile Ser Asn Asp Asn Thr Ser Tyr Arg Leu Ile Ser Cys Asn                 165 170 175 Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile             180 185 190 Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn         195 200 205 Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Lys Asn Val Ser Thr Val     210 215 220 Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu 225 230 235 240 Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser Glu Asn Leu                 245 250 255 Thr Asp Asn Gly Lys Thr Ile Ile Val Gln Leu Asn Glu Ser Val His             260 265 270 Ile Asn Cys Thr Arg Pro Ser Asn Asn Thr Arg Lys Ser Ile His Ile         275 280 285 Gly Pro Gly Lys Ala Phe Tyr Ala Thr Gly Gln Ile Ile Gly Asp Ile     290 295 300 Arg Gln Ala His Cys Asn Ile Ser Glu Lys Gln Trp Asn Lys Thr Leu 305 310 315 320 Ser Gln Ile Val Lys Lys Leu Arg Glu Gln Phe Lys Asn Lys Thr Ile                 325 330 335 Val Phe Asn Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ser             340 345 350 Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr Gln Leu Phe         355 360 365 Asn Thr Thr Trp Asn Trp Asn Asp Thr Glu Gly Ser Asn Asn Thr Glu     370 375 380 Arg Asn Glu Arg Asn Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Val 385 390 395 400 Asn Arg Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser                 405 410 415 Gly Pro Ile Ser Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg             420 425 430 Asp Gly Gly Leu Pro Asn Asn Thr Glu Thr Phe Arg Pro Glu Gly Gly         435 440 445 Asn Met Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val     450 455 460 Lys Ile Glu Pro Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val 465 470 475 480 Val Gln Arg Glu Lys Arg                 485 <210> 103 <211> 1610 <212> DNA <213> Human immunodeficiency virus type 1 <400> 103 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tatcagcact 60 ggtggaaatg gggcacgatg ctccttggaa tgttgatgat ctgtagtgct gcagaacaat 120 tgtgggttac agtctattat ggggtacctg tgtggaagga agcaaagacc actctattct 180 gtgcatcaga tgctaaagca tatgaaacag aggtacataa tgtttgggcc gcacatgcct 240 gtgtacccac agaccccaac ccacaagaag tagtattggc aaatgtgaca gaaaatttta 300 atatgtggga caacaacaag gtagaacaga tgcaggagga tataatcagt ttatgggatg 360 aaggcctaaa gccatgtgta aaattaaccc cactctgtat tactctaaat tgcactgacc 420 cctgtgatgc tcaaaatagc actcgaagtt gcacttattt gaatgatacg gtggaagagg 480 agagaggaca aataagaaat tgctctttca atatctccac aaagctagaa aatagaaggc 540 agacaggata tgcagttttt gataaacttg atttagtacc agtagatggt ggtaataata 600 ctgtcagata taggttgata aattgtaaca cctcagtcat tacacaagca tgtccaaagg 660 tatcctttga accaattccc atacattatt gtaccccagc tggttttgcg attctaaagt 720 gtaatgataa gaagttcaat ggaacagggc catgcacaaa tgtcagcaca gtacaatgca 780 cacatggaat taggccagta gtgtcaactc aactgctgtt aaatggcagt ctggcagaag 840 aagaggtagt aattagatct aaaaatttca cagacaatac taaaactata atagtacagc 900 tgaatgaatc tgtacaaatt aattgtacaa gacccaacaa caatacaaga cagagtacac 960 ctatgggacc agggaaagca ctttacacaa cacagataat aggagacata agacaagcac 1020 attgtaacat tagtacaaaa gattggaatg acaccttaaa aaagatagtt acaaaattag 1080 aagaacaatt tgaaaataaa acaataagct ttaatcaatc ctcaggaggg gacccagaaa 1140 ttgtaaagca cagttttaat tgtggagggg aattcttcta ctgtgataca acaaaactat 1200 ttaatagtac ttggcctgca agtatcaatt ataccactgg agtaaatatc actggagtta 1260 tcacactccc atgtagaata aaacaaatta taaacaggtg gcagggagga ggaaaggcaa 1320 tgtatgctcc tcccatcagt ggaccaatta gatgttcatc aaatattaca gggctgctat 1380 taacaagaga tggtggtgat gacaataatg gggctgagac ctttagacct ggaggaggag 1440 atatgaggga caattggaga agtgaattat ataaatataa agtagtaaaa attgaaccat 1500 taggagtagc acccaccaag gcaaagagaa gagtggtgca gagagaaaaa agagcagtgg 1560 gaacactagg agctatgttc cttgggttct tgggagcagc aggaagcact 1610 <210> 104 <211> 483 <212> PRT <213> Human immunodeficiency virus type 1 <400> 104 Ser Ala Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Lys Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Glu Thr Glu Val His Asn Val Trp Ala Ala His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Ala Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Asp Asn Asn Lys Val Glu Gln Met Gln Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Glu Gly Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Ile Thr Leu Asn Cys Thr Asp Pro Cys Asp Ala Gln Asn Ser             100 105 110 Thr Arg Ser Cys Thr Tyr Leu Asn Asp Thr Val Glu Glu Glu Arg Gly         115 120 125 Gln Ile Arg Asn Cys Ser Phe Asn Ile Ser Thr Lys Leu Glu Asn Arg     130 135 140 Arg Gln Thr Gly Tyr Ala Val Phe Asp Lys Leu Asp Leu Val Pro Val 145 150 155 160 Asp Gly Gly Asn Asn Thr Val Arg Tyr Arg Leu Ile Asn Cys Asn Thr                 165 170 175 Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro             180 185 190 Ile His Tyr Cys Thr Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp         195 200 205 Lys Lys Phe Asn Gly Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln     210 215 220 Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn 225 230 235 240 Gly Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser Lys Asn Phe Thr                 245 250 255 Asp Asn Thr Lys Thr Ile Ile Val Gln Leu Asn Glu Ser Val Gln Ile             260 265 270 Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Gln Ser Thr Pro Met Gly         275 280 285 Pro Gly Lys Ala Leu Tyr Thr Thr Gln Ile Ile Gly Asp Ile Arg Gln     290 295 300 Ala His Cys Asn Ile Ser Thr Lys Asp Trp Asn Asp Thr Leu Lys Lys 305 310 315 320 Ile Val Thr Lys Leu Glu Glu Gln Phe Glu Asn Lys Thr Ile Ser Phe                 325 330 335 Asn Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Lys His Ser Phe Asn             340 345 350 Cys Gly Gly Glu Phe Phe Tyr Cys Asp Thr Thr Lys Leu Phe Asn Ser         355 360 365 Thr Trp Pro Ala Ser Ile Asn Tyr Thr Thr Gly Val Asn Ile Thr Gly     370 375 380 Val Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Arg Trp Gln 385 390 395 400 Gly Gly Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly Pro Ile Arg                 405 410 415 Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asp             420 425 430 Asp Asn Asn Gly Ala Glu Thr Phe Arg Pro Gly Gly Gly Asp Met Arg         435 440 445 Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu     450 455 460 Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg 465 470 475 480 Glu lys arg              <210> 105 <211> 1589 <212> DNA <213> Human immunodeficiency virus type 1 <400> 105 agaaagagca gaagacagtg gcaatgaaag tgagggagac caggaggaat tattgggact 60 tgtggagatg gggcacgatg ctccttggga tgttaatgat ctgtagtgct acagaacaat 120 tatgggtcac aatctattat ggggtacctg tgtggaaaga agcagatacc actctatttt 180 gtgcatcaga tgctaaagca tatgatacag agaaacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccctaac ccacaagaag tagtaatggc aaatgtgaca gaaaatttta 300 acatgtggaa aaataacatg gtagaacaga tgcagaagga tattatcagt ctatgggatg 360 aaagcttaaa accatgtgta aaattaaccc cactctgtat cactttaaat tgcaatactt 420 taaattgcac acataacaat aattgtagta gtttgagaga agaaatgaca aactgctcct 480 tcaatgccac ctcaaaattg agagataagg ttcggaaaca atatgcaatt ttttctaaac 540 ttgatgtggt aaaactagat agtaataata atgaaacaga atataggttg ataaattgta 600 acacctcagt cgttacacag gcctgtccaa aggtatcatt tgagccaatt cccatacatt 660 attgtgcccc ggctggtttt gcgattctaa agtgtaacaa taagacattc gatggaaaag 720 gaccatgtac aaatgtcagc acagtacaat gtacacatgg aattaggcca gtagtgtcaa 780 ctcaactgct gttaaatggc agtctagcag aagaagggat agtaattaga tctgacaata 840 tctcagacaa tactaaaacc ataatagtac agctgaatga atctgtagca attaattgtt 900 caagacccca caacaataca agaaaaagta tacatatagc accagggaga gccttttatg 960 caacaggaga cataatagga gatataagac aagcacattg taacattagt agaaaacaat 1020 ggaataaaac tttagaacag gtagctaaaa aattaagaga aaaatttgta aataaagcaa 1080 ttatctttaa aaactcctca ggaggggacc cagaaattgt aatgcacagt tttaattgta 1140 gaggggaatt tttctactgt aatacaacac cactgtttaa tgggacttgg aatggtacta 1200 atttgagtac taataaggag tcaaatgaca caatcatact ccaatgtaga ataaaacaaa 1260 ttataaacat gtggcaggaa gtaggaaaag caatgtatgc ccctcccatt gcaggacaaa 1320 ttaactgttc atcaaaaatt acagggctac tattaacaag agatggtagt agcacaaatg 1380 ggacaaatga gactgagatc ttcagacctg gaggaggaga tatgagggac aattggagaa 1440 gcgaattata taaatataaa gtagtaagag ttgaaccaat aggaatagca cccaccaagg 1500 caaagagaag agtggtgcag agagaaaaaa gagcagtggg aacgttagga gctatgttcc 1560 ttgggttctt gggagcagca ggaagcact 1589 <210> 106 <211> 476 <212> PRT <213> Human immunodeficiency virus type 1 <400> 106 Ser Ala Thr Glu Gln Leu Trp Val Thr Ile Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Asp Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Lys His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Met Ala Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met Gln Lys Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Ile Thr Leu Asn Cys Asn Thr Leu Asn Cys Thr His Asn Asn             100 105 110 Asn Cys Ser Ser Leu Arg Glu Glu Met Thr Asn Cys Ser Phe Asn Ala         115 120 125 Thr Ser Lys Leu Arg Asp Lys Val Arg Lys Gln Tyr Ala Ile Phe Ser     130 135 140 Lys Leu Asp Val Val Lys Leu Asp Ser Asn Asn Asn Glu Thr Glu Tyr 145 150 155 160 Arg Leu Ile Asn Cys Asn Thr Ser Val Val Thr Gln Ala Cys Pro Lys                 165 170 175 Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe             180 185 190 Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asp Gly Lys Gly Pro Cys         195 200 205 Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val     210 215 220 Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Gly Ile Val 225 230 235 240 Ile Arg Ser Asp Asn Ile Ser Asp Asn Thr Lys Thr Ile Ile Val Gln                 245 250 255 Leu Asn Glu Ser Val Ala Ile Asn Cys Ser Arg Pro His Asn Asn Thr             260 265 270 Arg Lys Ser Ile His Ile Ala Pro Gly Arg Ala Phe Tyr Ala Thr Gly         275 280 285 Asp Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn Ile Ser Arg Lys     290 295 300 Gln Trp Asn Lys Thr Leu Glu Gln Val Ala Lys Lys Leu Arg Glu Lys 305 310 315 320 Phe Val Asn Lys Ala Ile Ile Phe Lys Asn Ser Ser Gly Gly Asp Pro                 325 330 335 Glu Ile Val Met His Ser Phe Asn Cys Arg Gly Glu Phe Phe Tyr Cys             340 345 350 Asn Thr Thr Pro Leu Phe Asn Gly Thr Trp Asn Gly Thr Asn Leu Ser         355 360 365 Thr Asn Lys Glu Ser Asn Asp Thr Ile Ile Leu Gln Cys Arg Ile Lys     370 375 380 Gln Ile Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro 385 390 395 400 Pro Ile Ala Gly Gln Ile Asn Cys Ser Ser Lys Ile Thr Gly Leu Leu                 405 410 415 Leu Thr Arg Asp Gly Ser Ser Thr Asn Gly Thr Asn Glu Thr Glu Ile             420 425 430 Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu         435 440 445 Tyr Lys Tyr Lys Val Val Arg Val Glu Pro Ile Gly Ile Ala Pro Thr     450 455 460 Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg 465 470 475 <210> 107 <211> 1689 <212> DNA <213> Human immunodeficiency virus type 1 <400> 107 agaaagagca gaagacagtg gcaatgagag tgacggggat caggaagaat tacttatgga 60 gatggggcac cttattcctg gggatattga tgatctgtaa ggctgcagaa aacttgtggg 120 tcacagtcta ttatggggta cctgtgtgga aagacgcaac caccactcta ttttgtgcat 180 cagatgctaa agctgttgat acagaagtac acaatgtgtg ggccacacat gcctgtgtac 240 ccacagaccc aaacccacaa gaagtagtat tgtataatgt gacagaaaat tttaacatgt 300 ggaaaaataa catggtagaa cagatgcatg aggatataat cagtttatgg gatgaaagtc 360 taaagccatg tgtaaagcta accccactct gtgttacttt gaattgcact gatgaattga 420 atatcaatac taataatacc tgtagtaata ccagtagtgg cactaataat accagtaatt 480 gcactaatgc tgagtcgact atcatcagta ccagtaatag tagcaatacc agaaatatca 540 gtgatagtag caagatagag aaaggagaaa taaaaaactg tactttcaat atcaccacaa 600 gcataagaga taaggtgcag aaagaatatg cactgtttta taaacttgat gtagtaccaa 660 caggtagtga caatactagc tataggttga taagttgtaa tacctcagtc attacacagg 720 cctgtccaaa ggtaaccttt gagccaattc ctatacatta ttgtgccccg gctggttatg 780 cgattgtaaa gtgcaacaat aagacattca gtggaaaagg accatgtaaa aatgtcagca 840 cagtacaatg cacacatggg attaagccag tagtatcaac tcagttgctg ttaaatggca 900 gtctggcaga aaaagatata gtaattagat ctgacaactt ctcaaacaat gctaaaacca 960 taatagtgca gctgaacaca tctgtagaaa ttaattgtac aagacccagc aacaatacaa 1020 gaaaaagtat tcatatagga ccagggagag cattttatgc aacagatata ataggagata 1080 taagacaagc acattgtaac attagtgaag aaaattggta taaaactcta aagcaggtag 1140 ctatgaaatt aggagaacag tttcagaata aaaaaatagt ctttaatcaa tcctcaggag 1200 gggacccaga aattgtaatg cacagtttta attgtggagg ggaatttttc ttctgtagta 1260 catcacaact gtttaatagt acttggaatt atagtacttg ggatgaaata gaaaataaaa 1320 ctcaaggaaa tggcacactc acactcccat gcagaataaa acaaattgta aacatgtggc 1380 aggaagtagg aaaagcaatg tatgcccctc ctatcaaagg aaatattaca tgttcatcaa 1440 agattacagg gttgctatta acaagagatg gtggtaagac taatatcaat ggcaccgaga 1500 tcttcagacc aggaggagga gatatgaggg acaattggag aagtgaacta tataaatata 1560 aagtagtaaa aattgaacca ttaggaatag cacccaccaa ggcaaagaga agagtggtgc 1620 agagagaaaa aagagcagtg ggaataggag ctatgttcct tgggttcttg ggaggcagca 1680 ggaagcact 1689 <210> 108 <211> 512 <212> PRT <213> Human immunodeficiency virus type 1 <400> 108 Lys Ala Ala Glu Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Asp Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Val Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Tyr Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Glu Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Glu Leu Asn Ile Asn Thr Asn             100 105 110 Asn Thr Cys Ser Asn Thr Ser Ser Gly Thr Asn Asn Thr Ser Asn Cys         115 120 125 Thr Asn Ala Glu Ser Thr Ile Ile Ser Thr Ser Asn Ser Ser Asn Thr     130 135 140 Arg Asn Ile Ser Asp Ser Ser Lys Ile Glu Lys Gly Glu Ile Lys Asn 145 150 155 160 Cys Thr Phe Asn Ile Thr Thr Ser Ile Arg Asp Lys Val Gln Lys Glu                 165 170 175 Tyr Ala Leu Phe Tyr Lys Leu Asp Val Val Pro Thr Gly Ser Asp Asn             180 185 190 Thr Ser Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val Ile Thr Gln Ala         195 200 205 Cys Pro Lys Val Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro     210 215 220 Ala Gly Tyr Ala Ile Val Lys Cys Asn Asn Lys Thr Phe Ser Gly Lys 225 230 235 240 Gly Pro Cys Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Lys                 245 250 255 Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Lys             260 265 270 Asp Ile Val Ile Arg Ser Asp Asn Phe Ser Asn Asn Ala Lys Thr Ile         275 280 285 Ile Val Gln Leu Asn Thr Ser Val Glu Ile Asn Cys Thr Arg Pro Ser     290 295 300 Asn Asn Thr Arg Lys Ser Ile His Ile Gly Pro Gly Arg Ala Phe Tyr 305 310 315 320 Ala Thr Asp Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn Ile Ser                 325 330 335 Glu Glu Asn Trp Tyr Lys Thr Leu Lys Gln Val Ala Met Lys Leu Gly             340 345 350 Glu Gln Phe Gln Asn Lys Lys Ile Val Phe Asn Gln Ser Ser Gly Gly         355 360 365 Asp Pro Glu Ile Val Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe     370 375 380 Phe Cys Ser Thr Ser Gln Leu Phe Asn Ser Thr Trp Asn Tyr Ser Thr 385 390 395 400 Trp Asp Glu Ile Glu Asn Lys Thr Gln Gly Asn Gly Thr Leu Thr Leu                 405 410 415 Pro Cys Arg Ile Lys Gln Ile Val Asn Met Trp Gln Glu Val Gly Lys             420 425 430 Ala Met Tyr Ala Pro Pro Ile Lys Gly Asn Ile Thr Cys Ser Ser Lys         435 440 445 Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Lys Thr Asn Ile Asn     450 455 460 Gly Thr Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp 465 470 475 480 Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly                 485 490 495 Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg             500 505 510 <210> 109 <211> 1616 <212> DNA <213> Human immunodeficiency virus type 1 <400> 109 agaaagagca gaagacagtg gcaatgagag tgatggggat caggaggaat tatcagcact 60 tgtggagatg gggcaccatg ctccttggga tgttgatgat ctgtaaaatc actacaggaa 120 aaacgtgggt cacagtctat tatggggtac ctgtgtggaa agaagcaact accactctat 180 tttgtgcatc agatgctaaa gcatatgata cagaggtaca taatgtttgg gccacacatg 240 cctgtgtacc cacagacccc aacccacaaa aaatagtaat ggtaaatgtg acagaggaat 300 ttaacatgtg gaaaaataac atggtagaac agatgcatga ggatataatc agtttatggg 360 atcagagcct aaagccatgt gtaaaattaa ccccactctg cgttacttta aattgcaatg 420 atactacgga gagaaattgc actggtcccg atggtagaaa aataaattgc actgaagtga 480 aaaattgctc tctcaatatc accacaaaca taagagataa ggtgcagaaa gaatatgcac 540 ttttttatag aactgatgtg gtgccaatag ataataataa tactagtacc agcagtcata 600 gctataggtt gataagttgt aatacctcag tccttacaca gacctgtcca aaagtatcct 660 ttcagccaat tcccatacat tattgtgccc cggctggttt tgcgattcta aaatgtaaca 720 ataggacatt caatggaaaa ggagaatgtg gtaatgtcag cacagtacaa tgtacacatg 780 gaattaagcc agtagtatca actcagctgc tgctaagtgg cagtctagca gaacaagaga 840 tagtgcttag atctgacaac ttctcagaca atgctaaaac cataatagta cagctgacta 900 aacctgtaga aattaattgt acacgaccca acaacaatac aagaaaaagt atagctatag 960 gaccagggag agcatttatt gcaacaggag acataatagg agatataaga caggcacatt 1020 gtaacattag taaagtagca tggaataaca ctatagaaga ggtagcaaga aaattaagca 1080 aacaatttgg gaatagatca ataaccttta atcaatcctc aggaggggac ccagaaattg 1140 taatgcacag ttttaattgt ggaggggaat ttttctactg taatacaaca ggactattta 1200 gtagtacttg gaatgttact gataattgga atgctactga agaggcaaat accactaggg 1260 taaatatcac actcccatgc agaataagac aaattgtaaa catgtggcag gaagtaggaa 1320 aagcaatgta tgcccctccc atcagaggac aaattagttg ctcatcaaat attacaggac 1380 tgatattaac aagagatggt ggtaaccaga gcaacgagac gacccctgag atctttagac 1440 ctggaggagg agatatgagg gacaattgga gaagtgaatt atataaatat aaagtagtaa 1500 aaattgaacc tataggaata gcacccacca aggcaaagag aagagtggtg cagagagaaa 1560 aaagaggggt actaggagct atgttccttg ggttcttggg agcagcagga agcact 1616 <210> 110 <211> 487 <212> PRT <213> Human immunodeficiency virus type 1 <400> 110 Lys Ile Thr Thr Gly Lys Thr Trp Val Thr Val Tyr Tyr Gly Val Pro 1 5 10 15 Val Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys             20 25 30 Ala Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val         35 40 45 Pro Thr Asp Pro Asn Pro Gln Lys Ile Val Met Val Asn Val Thr Glu     50 55 60 Glu Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp 65 70 75 80 Ile Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr                 85 90 95 Pro Leu Cys Val Thr Leu Asn Cys Asn Asp Thr Thr Glu Arg Asn Cys             100 105 110 Thr Gly Pro Asp Gly Arg Lys Ile Asn Cys Thr Glu Val Lys Asn Cys         115 120 125 Ser Leu Asn Ile Thr Thr Asn Ile Arg Asp Lys Val Gln Lys Glu Tyr     130 135 140 Ala Leu Phe Tyr Arg Thr Asp Val Val Pro Ile Asp Asn Asn Asn Thr 145 150 155 160 Ser Thr Ser Ser His Ser Tyr Arg Leu Ile Ser Cys Asn Thr Ser Val                 165 170 175 Leu Thr Gln Thr Cys Pro Lys Val Ser Phe Gln Pro Ile Pro Ile His             180 185 190 Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Arg Thr         195 200 205 Phe Asn Gly Lys Gly Glu Cys Gly Asn Val Ser Thr Val Gln Cys Thr     210 215 220 His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Ser Gly Ser 225 230 235 240 Leu Ala Glu Gln Glu Ile Val Leu Arg Ser Asp Asn Phe Ser Asp Asn                 245 250 255 Ala Lys Thr Ile Ile Val Gln Leu Thr Lys Pro Val Glu Ile Asn Cys             260 265 270 Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Ala Ile Gly Pro Gly         275 280 285 Arg Ala Phe Ile Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala     290 295 300 His Cys Asn Ile Ser Lys Val Ala Trp Asn Asn Thr Ile Glu Glu Val 305 310 315 320 Ala Arg Lys Leu Ser Lys Gln Phe Gly Asn Arg Ser Ile Thr Phe Asn                 325 330 335 Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys             340 345 350 Gly Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gly Leu Phe Ser Ser Thr         355 360 365 Trp Asn Val Thr Asp Asn Trp Asn Ala Thr Glu Glu Ala Asn Thr Thr     370 375 380 Arg Val Asn Ile Thr Leu Pro Cys Arg Ile Arg Gln Ile Val Asn Met 385 390 395 400 Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Gln                 405 410 415 Ile Ser Cys Ser Ser Asn Ile Thr Gly Leu Ile Leu Thr Arg Asp Gly             420 425 430 Gly Asn Gln Ser Asn Glu Thr Thr Pro Glu Ile Phe Arg Pro Gly Gly         435 440 445 Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val     450 455 460 Val Lys Ile Glu Pro Ile Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg 465 470 475 480 Val Val Gln Arg Glu Lys Arg                 485 <210> 111 <211> 1694 <212> DNA <213> Human immunodeficiency virus type 1 <400> 111 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tgtcactcct 60 ggagatgggg caccatgctc ctatggagat ggggcaccat gctccttggg ttgttaatga 120 tgatctgtaa tgctaaagaa gaaaaaacgt gggtcacagt atattatggg gtacctgtgt 180 ggaaagaagc gaccaccact ctattttgtg catcagatgc taaagcatat gacacagagg 240 tacataatgt ttgggccaca catgcctgtg tacctacaga ccccgaccca caggaaatat 300 tcttggaaaa tgtgacagaa aattttaaca tgtggaaaaa taacatggta gaacagatgc 360 atgaggatat aatcagtttg tgggatcaaa gcctaaagcc atgtgtaaaa ttaaccccac 420 tctgtgttac gttaaattgc actaatgtga ggattactag cataaattgc actgatgcga 480 gtagtaatag cactggtgtg gaaaaaacta ctagcactaa tggggggaat gttactattt 540 gtaatactac tgaggagata aaaaactgct ccttcaacat caccaccaac atgaaagata 600 agatacagaa gacatatgca ctgttttata aacttgatgt agaaccaata gataagggga 660 atgagaatag caccagctat agggtgataa gttgtaacac ttcaaccatt acacaggcct 720 gtccaaaggt atcctttgag ccaattccta tacattattg tgccccggct ggttttgcga 780 ttctaaaatg tagagataaa aggtttaatg gaacaggacc atgtacaaat gtcagcacag 840 tacaatgtac acatggaatt aaaccagtag tatcaactca actgctgtta aatggcagtc 900 tagcagaaga agagatagta cttagatctg aaaatttctc gaacaatgct aaaaacatat 960 taatacagct aaaagaacct gtagaaatta attgtacaag acccaacaac aatacaagaa 1020 aaggtataca tataggacca ggaagagcat tttatggaac agatataata ggagatataa 1080 gacaagcaca ttgtaacatt agcagagaaa aatggaatag cactttaagt cagatagttg 1140 ataaattaag agaacaatat gggaaaaata aaacaataat ctttgatcaa ccatcaggag 1200 gggacccaga aattgtaacg cacagtttta attgtggagg agaatttttc tactgtaatt 1260 caacacaact gtttaatagc acttggtatg ataatagtac ttggaatgag aataaaaatc 1320 acactaaaaa tgacacaatc acgctcccat gcagaataaa gcaatttata aacatgtggc 1380 aggaagtagg aaaagcaatg tatgcccctc ccatcagagg acaaattaaa tgctcatcaa 1440 atattacagg gctaataata acaagagatg gggggaacaa caacagcgag accttcaaca 1500 acgagacctt cagacctgga ggaggaaata tgaaggacaa ttggagaagt gaattatata 1560 aatataaagt agtaagaatt gagccattag gagtagcacc caccagggca aagaggagag 1620 tggtgcagag agaaaaaaga gcagtgggaa taggagctgt gttccttggg ttcttgggag 1680 cagcaggaag cact 1694 <210> 112 <211> 504 <212> PRT <213> Human immunodeficiency virus type 1 <400> 112 Asn Ala Lys Glu Glu Lys Thr Trp Val Thr Val Tyr Tyr Gly Val Pro 1 5 10 15 Val Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys             20 25 30 Ala Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val         35 40 45 Pro Thr Asp Pro Asp Pro Gln Glu Ile Phe Leu Glu Asn Val Thr Glu     50 55 60 Asn Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp 65 70 75 80 Ile Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr                 85 90 95 Pro Leu Cys Val Thr Leu Asn Cys Thr Asn Val Arg Ile Thr Ser Ile             100 105 110 Asn Cys Thr Asp Ala Ser Ser Asn Ser Thr Gly Val Glu Lys Thr Thr         115 120 125 Ser Thr Asn Gly Gly Asn Val Thr Ile Cys Asn Thr Thr Glu Glu Ile     130 135 140 Lys Asn Cys Ser Phe Asn Ile Thr Thr Asn Met Lys Asp Lys Ile Gln 145 150 155 160 Lys Thr Tyr Ala Leu Phe Tyr Lys Leu Asp Val Glu Pro Ile Asp Lys                 165 170 175 Gly Asn Glu Asn Ser Thr Ser Tyr Arg Val Ile Ser Cys Asn Thr Ser             180 185 190 Thr Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile         195 200 205 His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Arg Asp Lys     210 215 220 Arg Phe Asn Gly Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys 225 230 235 240 Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly                 245 250 255 Ser Leu Ala Glu Glu Glu Ile Val Leu Arg Ser Glu Asn Phe Ser Asn             260 265 270 Asn Ala Lys Asn Ile Leu Ile Gln Leu Lys Glu Pro Val Glu Ile Asn         275 280 285 Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Gly Ile His Ile Gly Pro     290 295 300 Gly Arg Ala Phe Tyr Gly Thr Asp Ile Ile Gly Asp Ile Arg Gln Ala 305 310 315 320 His Cys Asn Ile Ser Arg Glu Lys Trp Asn Ser Thr Leu Ser Gln Ile                 325 330 335 Val Asp Lys Leu Arg Glu Gln Tyr Gly Lys Asn Lys Thr Ile Ile Phe             340 345 350 Asp Gln Pro Ser Gly Gly Asp Pro Glu Ile Val Thr His Ser Phe Asn         355 360 365 Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr Gln Leu Phe Asn Ser     370 375 380 Thr Trp Tyr Asp Asn Ser Thr Trp Asn Glu Asn Lys Asn His Thr Lys 385 390 395 400 Asn Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Phe Ile Asn Met                 405 410 415 Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Gln             420 425 430 Ile Lys Cys Ser Ser Asn Ile Thr Gly Leu Ile Ile Thr Arg Asp Gly         435 440 445 Gly Asn Asn Asn Ser Glu Thr Phe Asn Asn Glu Thr Phe Arg Pro Gly     450 455 460 Gly Gly Asn Met Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys 465 470 475 480 Val Val Arg Ile Glu Pro Leu Gly Val Ala Pro Thr Arg Ala Lys Arg                 485 490 495 Arg Val Val Gln Arg Glu Lys Arg             500 <210> 113 <211> 1685 <212> DNA <213> Human immunodeficiency virus type 1 <400> 113 agaaagagca gaagacagtg gcaatgagag tgaaggggac caagacgaat tatcagcact 60 tatggagatg gggcatcatg ctcctgggga tattgatgat ctgtagtgct acagaacaat 120 ggtgggtcac agtctattat ggagtacctg tgtggagaga tgcaaatacc actctatttt 180 gtgcatcaga ttctaaagca tatgctacag aggtacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaaa taaacttgga aaatgtaaca gaagagttta 300 acatatggaa aaataacatg gtagaacaaa tgcatgagga tataatcagt ttatgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cactctgtgt tactttaaat tgcactgatt 420 acaatggtac tcataccaat actactaata ccactagtat ttatggggaa aagatggaaa 480 taggagaagt aaagaaatgc tctttcaatg ctaccacaat cataagagat aaggtggaca 540 aagaagaagc acttttttat aaacttgata tagtaccaat agatggtaat aatgagacta 600 acatagttaa taatgggact aataatacta gtaccaacta taccagctat aggctaataa 660 attgtaacac ctcagtcatt acacaggcct gtccagaggt atcctttgag ccaattccca 720 tacattattg tgccccggct ggttttgcga ttctaaagtg taaagagaag gcgttcaatg 780 gaagtgggcc atgtaaaaat gtcagctcag tacaatgtac acatggaatt aagccagtag 840 tatcaactca attgccgtta aatggcagtc tagcagaaga agaagtagta attagatctg 900 aaaatttcac aaacaatgct aaaaccataa tagtacagct gaaagaagct gtaaacatta 960 gttgtataag gcccaacaac aatacaagaa aaagtatacc tataggacca gggagagcat 1020 tttatgcaac aggagacata ataggagata taggacaagc acattgtaac cttagtagaa 1080 caaattggaa taaaacttta caacagatag ctacaaaatt aggagaaaag tttaataaaa 1140 caacaataat ctttaatcaa tcctcaggag gggacccaga aattgtaatg cacagtttta 1200 tttgtggagg ggaatttttc tactgtaata caacacaact gtttaatagt acttggaact 1260 gtactgagaa tgggaattgt acactggtta ccggtacttg gcctgacagg ccaaatagaa 1320 ctggagaaaa tgacacaatc acactcccat gcagaataaa acaaatcata aacctgtggc 1380 aggaagtagg aaaagcaatg tatgcctctc ccatccaggg actaattaat tgtacatcaa 1440 atattacagg gctgctatta acaagagatg gtggtaccca tagtagacag aatgagacct 1500 tcagacctga aggaggaaat atgaaagaca attggagaag tgaattatat aaatataaag 1560 tagtaagaat tgaaccatta ggagtagcac ccaccaaggc aaagagaaga gtggtgcaga 1620 gagaaaaaag agcagtggga ttgggagcta tgatccttgg gttcttggga gcagcaggaa 1680 gcact 1685 <210> 114 <211> 509 <212> PRT <213> Human immunodeficiency virus type 1 <400> 114 Ser Ala Thr Glu Gln Trp Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Arg Asp Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ser Lys Ala             20 25 30 Tyr Ala Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Ile Asn Leu Glu Asn Val Thr Glu Glu     50 55 60 Phe Asn Ile Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Tyr Asn Gly Thr His Thr Asn             100 105 110 Thr Thr Asn Thr Thr Ser Ile Tyr Gly Glu Lys Met Glu Ile Gly Glu         115 120 125 Val Lys Lys Cys Ser Phe Asn Ala Thr Thr Ile Ile Arg Asp Lys Val     130 135 140 Asp Lys Glu Glu Ala Leu Phe Tyr Lys Leu Asp Ile Val Pro Ile Asp 145 150 155 160 Gly Asn Asn Glu Thr Asn Ile Val Asn Asn Gly Thr Asn Asn Thr Ser                 165 170 175 Thr Asn Tyr Thr Ser Tyr Arg Leu Ile Asn Cys Asn Thr Ser Val Ile             180 185 190 Thr Gln Ala Cys Pro Glu Val Ser Phe Glu Pro Ile Pro Ile His Tyr         195 200 205 Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Lys Glu Lys Ala Phe     210 215 220 Asn Gly Ser Gly Pro Cys Lys Asn Val Ser Ser Val Gln Cys Thr His 225 230 235 240 Gly Ile Lys Pro Val Val Ser Thr Gln Leu Pro Leu Asn Gly Ser Leu                 245 250 255 Ala Glu Glu Glu Val Val Ile Arg Ser Glu Asn Phe Thr Asn Asn Ala             260 265 270 Lys Thr Ile Ile Val Gln Leu Lys Glu Ala Val Asn Ile Ser Cys Ile         275 280 285 Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Pro Ile Gly Pro Gly Arg     290 295 300 Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Gly Gln Ala His 305 310 315 320 Cys Asn Leu Ser Arg Thr Asn Trp Asn Lys Thr Leu Gln Gln Ile Ala                 325 330 335 Thr Lys Leu Gly Glu Lys Phe Asn Lys Thr Thr Ile Ile Phe Asn Gln             340 345 350 Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Ile Cys Gly         355 360 365 Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn Ser Thr Trp     370 375 380 Asn Cys Thr Glu Asn Gly Asn Cys Thr Leu Val Thr Gly Thr Trp Pro 385 390 395 400 Asp Arg Pro Asn Arg Thr Gly Glu Asn Asp Thr Ile Thr Leu Pro Cys                 405 410 415 Arg Ile Lys Gln Ile Ile Asn Leu Trp Gln Glu Val Gly Lys Ala Met             420 425 430 Tyr Ala Ser Pro Ile Gln Gly Leu Ile Asn Cys Thr Ser Asn Ile Thr         435 440 445 Gly Leu Leu Leu Thr Arg Asp Gly Gly Thr His Ser Arg Gln Asn Glu     450 455 460 Thr Phe Arg Pro Glu Gly Gly Asn Met Lys Asp Asn Trp Arg Ser Glu 465 470 475 480 Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Pro Leu Gly Val Ala Pro                 485 490 495 Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg             500 505 <210> 115 <211> 1632 <212> DNA <213> Human immunodeficiency virus type 1 <400> 115 agaaagagca aaacagtggc aatgaaagtg aaggggacca ggatgaattg tcagcgctgg 60 tggtggacat ggggcacgat gctccttggg atgttgatga tctgtagtgc tgcagaaaag 120 ttgtgggtca cagtctatta tggggtacct gtgtggaaag aagcaaccac cactctattt 180 tgtgcatcag atgctaaagc atataagaca gaaaagcata atgtctgggc cacacatgcc 240 tgtgtaccca caaaccccaa cccacaagaa gtagtaatgg aaaatgtaac agaatatttt 300 aacatgtgga aaaataacat ggtagaacag atgcaggagg atataatcag tttatgggat 360 caaagcctaa agccatgtgt aaaattaacc ccactctgtg taactttaac ttgtgtgaat 420 attactaact gtaagaataa tactaactgt aataatgata ctaacagtaa gaatgatact 480 cttaaggagg agatagggga aataaaaaac tgctctttca acgtcaccac agccataaga 540 gataaggtgc agaaagaata tgcattattt cataaacttg atgtagtaca aatagataat 600 gataatacta gtagtaatac ttctaagcct tataggttga taagttgtaa cacctcagtc 660 attacacagg cctgtccaaa ggtaaccttt gagccaattc ccatacatta ttgtgcctcg 720 gctggttttg cgattctaaa gtgtaacaat aagactttca atggaacagg accatgtaca 780 aatgtcagca cagtacaatg tacacatgga attaggccag tagtatcaac tcaactgttg 840 ttaaatgaca gcctagcaga aaaagaggca atagttagat ctgaaaattt cacaaacaac 900 gctaaaatca taatagtaca gctaaatgaa tctgtagaga ttaattgtac aagacccaac 960 aacaatacaa gaagaagtat acctatagga ccagggaaag cattttttac atcagaaata 1020 ataggagata taagaaaagc acactgtaac attagtggaa caaagtggaa tgccactttg 1080 cataaaatag ctataaaatt aagagaacaa tatggaaata aaacaatagt ctttaatcaa 1140 ccttcaggag gggacccaga agttgtaatg cacagtttta actgtggagg ggaatttttc 1200 tactgtgata caacacaact gtttaatagt acttggttta atagtacttg gccaaatatc 1260 acacttgaag aaaatatcac actcccatgc aaaataaaac aatttataaa catgtggcag 1320 gaagtaggaa aagcaatgta tgcccctccc atcagaggac aaattaactg ttcatcacag 1380 attacagggc tgctattaac aagagatggt ggtcagggta acaatactaa caacgacact 1440 gagattttca gaccaggggg aggagatatg agggacaatt ggagaagtga attatacaaa 1500 tataaagtag taagaattga gccattggga gtagcaccca ccaaggcaat gagaagagtg 1560 gtgcagagag aaaaaagagc aataggacta ggagcttttt tccttgggtt cttgggagca 1620 gcaggaagca ct 1632 <210> 116 <211> 491 <212> PRT <213> Human immunodeficiency virus type 1 <400> 116 Ser Ala Ala Glu Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Lys Thr Glu Lys His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asn Pro Asn Pro Gln Glu Val Val Met Glu Asn Val Thr Glu Tyr     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met Gln Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Thr Cys Val Asn Ile Thr Asn Cys Lys Asn Asn             100 105 110 Thr Asn Cys Asn Asn Asp Thr Asn Ser Lys Asn Asp Thr Leu Lys Glu         115 120 125 Glu Ile Gly Glu Ile Lys Asn Cys Ser Phe Asn Val Thr Thr Ala Ile     130 135 140 Arg Asp Lys Val Gln Lys Glu Tyr Ala Leu Phe His Lys Leu Asp Val 145 150 155 160 Val Gln Ile Asp Asn Asp Asn Thr Ser Ser Asn Thr Ser Lys Pro Tyr                 165 170 175 Arg Leu Ile Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys             180 185 190 Val Thr Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Ser Ala Gly Phe         195 200 205 Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys     210 215 220 Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val 225 230 235 240 Ser Thr Gln Leu Leu Leu Asn Asp Ser Leu Ala Glu Lys Glu Ala Ile                 245 250 255 Val Arg Ser Glu Asn Phe Thr Asn Asn Ala Lys Ile Ile Ile Val Gln             260 265 270 Leu Asn Glu Ser Val Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr         275 280 285 Arg Arg Ser Ile Pro Ile Gly Pro Gly Lys Ala Phe Phe Thr Ser Glu     290 295 300 Ile Ile Gly Asp Ile Arg Lys Ala His Cys Asn Ile Ser Gly Thr Lys 305 310 315 320 Trp Asn Ala Thr Leu His Lys Ile Ala Ile Lys Leu Arg Glu Gln Tyr                 325 330 335 Gly Asn Lys Thr Ile Val Phe Asn Gln Pro Ser Gly Gly Asp Pro Glu             340 345 350 Val Val Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asp         355 360 365 Thr Thr Gln Leu Phe Asn Ser Thr Trp Phe Asn Ser Thr Trp Pro Asn     370 375 380 Ile Thr Leu Glu Glu Asn Ile Thr Leu Pro Cys Lys Ile Lys Gln Phe 385 390 395 400 Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile                 405 410 415 Arg Gly Gln Ile Asn Cys Ser Ser Gln Ile Thr Gly Leu Leu Leu Thr             420 425 430 Arg Asp Gly Gly Gln Gly Asn Asn Thr Asn Asn Asp Thr Glu Ile Phe         435 440 445 Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr     450 455 460 Lys Tyr Lys Val Val Arg Ile Glu Pro Leu Gly Val Ala Pro Thr Lys 465 470 475 480 Ala Met Arg Arg Val Val Gln Arg Glu Lys Arg                 485 490 <210> 117 <211> 1679 <212> DNA <213> Human immunodeficiency virus type 1 <400> 117 agaaagagca gaagacagtg gcaatgagag tgatggggat caggaagagt tatcagcact 60 tgtggaaagg gggcaccttg ctccttggaa tattgatgat ctgtagtgct gcagaacaat 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga tgcaaccacc actttatttt 180 gtgcatcaga tgctaaagca tatgatacag aggtacacaa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaag tagtaatggg aaatgtgaca gaatatttta 300 acatgtggac aaataacatg gtagaacaga tgcatgagga tgtaatcagt ttatgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cactctgtgt tactttaaat tgcactaatt 420 tggtgaatac tacctgtaat gggactacta acaataatac tacctgtact gggactgcta 480 acaatgatac taataccaat agtactaggt gggtgtatca agcgatggca ggagaaataa 540 aaaactgctc tttcaatatc accacaaaca taagagataa gataaaaaaa gaatatgcac 600 tttttaatag acttgatata gtaccaatag atgatgagaa taagaatact ggcaatacta 660 ctagctatag gttgataagt tgtaacacct cagtcattac acaggcctgt ccaaaggtaa 720 cctttgaacc aattcccata cattattgtg ccccggctgg ttttgcgatt ctcaagtgta 780 atgataagaa gttcaatgga acaggaccat gtacaaatgt cagcacagta caatgtacac 840 atggaattag gccagtagta tcaactcaac tactattaaa tggcagtcta gcagaagaag 900 agacagtaat tagatctagc aatttctcga acaatgctaa aatcataata gtacagctga 960 atgaaactgt acgaattaat tgtacaagac ccaacaacaa tacaagaaga agtatacata 1020 taggaccagg gagagcattt tatgcaacag gagacataat aggagatata agacaagcac 1080 attgtaacat tagtggagaa gaatggagga gaactttaaa acggataact ataaaattag 1140 gagaacaatt taataaaaca aaaataagct ataaccaatc ctcaggaggg gacccagaaa 1200 ttgtaaggca cagttttaat tgtcaagggg aatttttcta ctgtgataca tcaggactgt 1260 ttaatagtac ttgggtgaag aatgatactt ggaatgagag tagtattagc aatggaacta 1320 tcacactccc atgcagaata aaacaaattg taaacatgtg gcaggaagta ggaagagcaa 1380 tgtatgcccc tcctatcaaa ggacaaatta attgtacatc gaatattaca gggctgctac 1440 taacaagaga tggtggtcag actaatagca ccaacaacga cactgagacc ttcagaccta 1500 caggaggaga tataagggac aattggagga gtgaattata taaatataaa gtagtaaaaa 1560 ttgaaccatt aggaatagca cccaccaggg caaaaagaag agtggtgcaa agagaaaaaa 1620 gagcagtggg aacgatggga gcgttgttcc ttgggttctt gggagcagca ggaagcact 1679 <210> 118 <211> 506 <212> PRT <213> Human immunodeficiency virus type 1 <400> 118 Ser Ala Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Asp Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Met Gly Asn Val Thr Glu Tyr     50 55 60 Phe Asn Met Trp Thr Asn Asn Met Val Glu Gln Met His Glu Asp Val 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asn Leu Val Asn Thr Thr Cys Asn             100 105 110 Gly Thr Thr Asn Asn Asn Thr Thr Cys Thr Gly Thr Ala Asn Asn Asp         115 120 125 Thr Asn Thr Asn Ser Thr Arg Trp Val Tyr Gln Ala Met Ala Gly Glu     130 135 140 Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Asn Ile Arg Asp Lys Ile 145 150 155 160 Lys Lys Glu Tyr Ala Leu Phe Asn Arg Leu Asp Ile Val Pro Ile Asp                 165 170 175 Asp Glu Asn Lys Asn Thr Gly Asn Thr Thr Ser Tyr Arg Leu Ile Ser             180 185 190 Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Thr Phe Glu         195 200 205 Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys     210 215 220 Cys Asn Asp Lys Lys Phe Asn Gly Thr Gly Pro Cys Thr Asn Val Ser 225 230 235 240 Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln Leu                 245 250 255 Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Thr Val Ile Arg Ser Ser             260 265 270 Asn Phe Ser Asn Asn Ala Lys Ile Ile Ile Val Gln Leu Asn Glu Thr         275 280 285 Val Arg Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Arg Ser Ile     290 295 300 His Ile Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly Asp Ile Ile Gly 305 310 315 320 Asp Ile Arg Gln Ala His Cys Asn Ile Ser Gly Glu Glu Trp Arg Arg                 325 330 335 Thr Leu Lys Arg Ile Thr Ile Lys Leu Gly Glu Gln Phe Asn Lys Thr             340 345 350 Lys Ile Ser Tyr Asn Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Arg         355 360 365 His Ser Phe Asn Cys Gln Gly Glu Phe Phe Tyr Cys Asp Thr Ser Gly     370 375 380 Leu Phe Asn Ser Thr Trp Val Lys Asn Asp Thr Trp Asn Glu Ser Ser 385 390 395 400 Ile Ser Asn Gly Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Val                 405 410 415 Asn Met Trp Gln Glu Val Gly Arg Ala Met Tyr Ala Pro Pro Ile Lys             420 425 430 Gly Gln Ile Asn Cys Thr Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg         435 440 445 Asp Gly Gly Gln Thr Asn Ser Thr Asn Asn Asp Thr Glu Thr Phe Arg     450 455 460 Pro Thr Gly Gly Asp Ile Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys 465 470 475 480 Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Ile Ala Pro Thr Arg Ala                 485 490 495 Lys Arg Arg Val Val Gln Arg Glu Lys Arg             500 505 <210> 119 <211> 1589 <212> DNA <213> Human immunodeficiency virus type 1 <400> 119 agaaagagca gaagacagtg gcaatgagag tgagggggat catgaggaat tacttgtgga 60 aatggggcat catgctcctt gggatattga tgatctgtag tgctacagac aaattgtggg 120 tcacagtcta ttatggggtg cctgtgtgga aagaagcatc caccactcta ttttgtgcat 180 cagatgctaa agcctatgat acagaggtac ataatgtttg ggccacacat gcctgtgtac 240 ccacagatcc caatccacac gaattagaat tggaaaatgt gacagaagat tttaacatgt 300 ggaaaaatga catggtcgaa cagatgcatg aggatataat cagtttatgg gatcaaagcc 360 taaaaccatg tgtaaaatta accccactct gtgttacttt aaattgcagt gatgctttaa 420 cttgcaatag gacatcaaat agcagtagta cttcaaattg cagtaactgg gaaccgatag 480 aagaaataaa aaattgctct ttcaatatta ccacaagcat agaaaataag atgcagaaaa 540 agtctgcatt ttttgatgcc cttgatgtag tacaaataga tgatactagt tataggttga 600 taaattgtaa cacctcagtc attacacagg cctgtccaaa gatatccttt gagccaattc 660 ccatacatta ttgtgccccg gctggttttg cgcttctaaa gtgtaaggat ccgaaattca 720 atggaacagg gccatgtaaa tatgctagct cagtacagtg tacacatgga attaggccgg 780 tagtatcaac tcaactgctg ctaaatggca gtctagcaga agaagatata gtaattagat 840 ctgccaattt ctcggacaac accaaagcca taatagtaca actaaaagaa cctgtaataa 900 ttaattgcac aagacccaac aacaatacaa gacaaagtgt acatatagga ccagggagcg 960 cactttatac aacagatata ataggagata taagaaaagc acattgtaac attagtagag 1020 cagactggac taaagcttta aaccagacag tcataaaatt aagagaacaa tttaagaata 1080 aaacaatagt ctttaatcaa tcctcaggag gggatccaga aattgtaatg cacactttta 1140 attgtggagg ggaatttttc tattgtaatt caacaaaact gtttaatagt acttggaatg 1200 ggactgaacc aggagagtca aatgacactg taatcatact cccatgcaga ataaaacaaa 1260 ttataaatat gtggcaggaa gtaggaaaag caatgtatgc ccctcccatc agaggacaaa 1320 ttagatgtac atcaaatatt acagggctgc tactaacaag agatggggga aatgagacca 1380 ctaaaaacgg gactgagacc ttcagacctg gaggaggaaa tatgaaggac aattggagaa 1440 gtgaattata taaatataaa gtggtaaaaa ttgaaccatt aggagtagca cccaccaagg 1500 caaaaagaag agtggtgcag agagaaaaaa gagcaatagg ggcattcgga gctatgttcc 1560 ttgggttctt gggagcagca ggaagcact 1589 <210> 120 <211> 478 <212> PRT <213> Human immunodeficiency virus type 1 <400> 120 Ser Ala Thr Asp Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Ser Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro His Glu Leu Glu Leu Glu Asn Val Thr Glu Asp     50 55 60 Phe Asn Met Trp Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Ser Asp Ala Leu Thr Cys Asn Arg Thr             100 105 110 Ser Asn Ser Ser Ser Thr Ser Asn Cys Ser Asn Trp Glu Pro Ile Glu         115 120 125 Glu Ile Lys Asn Cys Ser Phe Asn Ile Thr Thr Ser Ile Glu Asn Lys     130 135 140 Met Gln Lys Lys Ser Ala Phe Phe Asp Ala Leu Asp Val Val Gln Ile 145 150 155 160 Asp Asp Thr Ser Tyr Arg Leu Ile Asn Cys Asn Thr Ser Val Ile Thr                 165 170 175 Gln Ala Cys Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile His Tyr Cys             180 185 190 Ala Pro Ala Gly Phe Ala Leu Leu Lys Cys Lys Asp Pro Lys Phe Asn         195 200 205 Gly Thr Gly Pro Cys Lys Tyr Ala Ser Ser Val Gln Cys Thr His Gly     210 215 220 Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala 225 230 235 240 Glu Glu Asp Ile Val Ile Arg Ser Ala Asn Phe Ser Asp Asn Thr Lys                 245 250 255 Ala Ile Ile Val Gln Leu Lys Glu Pro Val Ile Ile Asn Cys Thr Arg             260 265 270 Pro Asn Asn Asn Thr Arg Gln Ser Val His Ile Gly Pro Gly Ser Ala         275 280 285 Leu Tyr Thr Thr Asp Ile Ile Gly Asp Ile Arg Lys Ala His Cys Asn     290 295 300 Ile Ser Arg Ala Asp Trp Thr Lys Ala Leu Asn Gln Thr Val Ile Lys 305 310 315 320 Leu Arg Glu Gln Phe Lys Asn Lys Thr Ile Val Phe Asn Gln Ser Ser                 325 330 335 Gly Gly Asp Pro Glu Ile Val Met His Thr Phe Asn Cys Gly Gly Glu             340 345 350 Phe Phe Tyr Cys Asn Ser Thr Lys Leu Phe Asn Ser Thr Trp Asn Gly         355 360 365 Thr Glu Pro Gly Glu Ser Asn Asp Thr Val Ile Ile Leu Pro Cys Arg     370 375 380 Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr 385 390 395 400 Ala Pro Pro Ile Arg Gly Gln Ile Arg Cys Thr Ser Asn Ile Thr Gly                 405 410 415 Leu Leu Leu Thr Arg Asp Gly Gly Asn Glu Thr Thr Lys Asn Gly Thr             420 425 430 Glu Thr Phe Arg Pro Gly Gly Gly Asn Met Lys Asp Asn Trp Arg Ser         435 440 445 Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val Ala     450 455 460 Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg 465 470 475 <210> 121 <211> 1616 <212> DNA <213> Human immunodeficiency virus type 1 <400> 121 agaaagagca gaagacagtg gcaatgaaag tgaaggggat caggaagaat tgtcagcgct 60 tgtggagatg gggcacgatg ctccttggga tgttaatgat atgtagtgct gcagagcaat 120 tgtgggtcac agtctattat ggggtacctg tgtggagaga agcaaacacc actctattct 180 gtgcctcaga tgctaaagca caggttgcag aggcacataa tgtatgggcc acacatgcct 240 gtgtacccac agaccctagc ccacaagaag tagtaatgga aaatgtgaca gaaaatttta 300 acatgtggaa aaataacatg gtagaacaga tgcatgagga tataatcagt ttatgggatc 360 aaagtctaaa gccatgtgtg aaattaaccc cactctgcgt tactttaaat tgcactaatg 420 tgggttgcac tggtaatact actggaccca attgtacttc tttgactgat cataatagta 480 atcttacttg gggaatggag aaaggagaaa taaaaaattg ctctttcaat gtcaccagta 540 taacaaataa gatgcagaaa gaatatgcac ttttttataa acttgatgta atgccaatgg 600 atagtacaga taatacaacg tatacactga taaattgtaa cccctcagtc attacacagg 660 cctgtccaaa ggtatctttt gaacccattc ctatacatta ttgtaccccg gctggttttg 720 cgattctaaa gtgtaatgat aagacattca atggatcagg accatgtaca aatgtcagta 780 cagtactatg tacacatgga attaggccag tagtgtcaac tcaactactg ttaaatggca 840 gtctagcaga agaggaggta atagtcaggt ccgagaattt ctcggacaat actaaaatca 900 taatagtaca gctgaataaa actgtagaaa ttaattgtac aagacccaat aacaatacaa 960 gaaaaagtat acatatagca ccaggaaaag cattctatgc aacaggtgat ataataggag 1020 atataagaca agcacattgt aacatcagtg aaacaaaatg ggtgaacact ttaaaacagg 1080 tagttacaaa attaagggaa caatatggga ataaaacaat agcctttaat caatcctcag 1140 gaggggatcc agaaattgta acgcatagtt ttaattgtgg aggagaattt ttctactgta 1200 atacatcacg gctgtttaat agtaattgga ctgggaatgg aacgactgag tcaggaaata 1260 gcacaatcat acttccatgc agaataaaac aaattataaa cagatggcag gaagtaggaa 1320 aagcaatgta tgccaatccc attagtggac caatcaactg ttcatcaaac attacagggc 1380 tgctattaac aagagatggt ggtaaagtga ccaatgacac caccgagacc ttcagacctt 1440 ggggtggaga tatgagggac aattggagaa gtgaactata taaatataaa gtagtaagaa 1500 ttgagccatt aggactagca cccaccaggg caaagagaag agtggtgcag agagaaaaga 1560 gagcaataac attaggagct atgttccttg ggttcttggg agcagcagga agcact 1616 <210> 122 <211> 486 <212> PRT <213> Human immunodeficiency virus type 1 <400> 122 Ser Ala Ala Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Arg Glu Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Gln Val Ala Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Ser Pro Gln Glu Val Val Met Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asn Val Gly Cys Thr Gly Asn Thr             100 105 110 Thr Gly Pro Asn Cys Thr Ser Leu Thr Asp His Asn Ser Asn Leu Thr         115 120 125 Trp Gly Met Glu Lys Gly Glu Ile Lys Asn Cys Ser Phe Asn Val Thr     130 135 140 Ser Ile Thr Asn Lys Met Gln Lys Glu Tyr Ala Leu Phe Tyr Lys Leu 145 150 155 160 Asp Val Met Pro Met Asp Ser Thr Asp Asn Thr Thr Tyr Thr Leu Ile                 165 170 175 Asn Cys Asn Pro Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe             180 185 190 Glu Pro Ile Pro Ile His Tyr Cys Thr Pro Ala Gly Phe Ala Ile Leu         195 200 205 Lys Cys Asn Asp Lys Thr Phe Asn Gly Ser Gly Pro Cys Thr Asn Val     210 215 220 Ser Thr Val Leu Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln 225 230 235 240 Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Ile Val Arg Ser                 245 250 255 Glu Asn Phe Ser Asp Asn Thr Lys Ile Ile Ile Val Gln Leu Asn Lys             260 265 270 Thr Val Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser         275 280 285 Ile His Ile Ala Pro Gly Lys Ala Phe Tyr Ala Thr Gly Asp Ile Ile     290 295 300 Gly Asp Ile Arg Gln Ala His Cys Asn Ile Ser Glu Thr Lys Trp Val 305 310 315 320 Asn Thr Leu Lys Gln Val Val Thr Lys Leu Arg Glu Gln Tyr Gly Asn                 325 330 335 Lys Thr Ile Ala Phe Asn Gln Ser Ser Gly Gly Asp Pro Glu Ile Val             340 345 350 Thr His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser         355 360 365 Arg Leu Phe Asn Ser Asn Trp Thr Gly Asn Gly Thr Thr Glu Ser Gly     370 375 380 Asn Ser Thr Ile Ile Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Arg 385 390 395 400 Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Asn Pro Ile Ser Gly Pro                 405 410 415 Ile Asn Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly             420 425 430 Gly Lys Val Thr Asn Asp Thr Thr Glu Thr Phe Arg Pro Trp Gly Gly         435 440 445 Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val     450 455 460 Arg Ile Glu Pro Leu Gly Leu Ala Pro Thr Arg Ala Lys Arg Arg Val 465 470 475 480 Val Gln Arg Glu Lys Arg                 485 <210> 123 <211> 1610 <212> DNA <213> Human immunodeficiency virus type 1 <400> 123 agaaagagca gaagacagtg gcaatgagag tgaaggagat caggaagaat tggcagcgct 60 tgtggagatg gggcatgatg ctccttggga tgttgatgat cagtagtgct gaagaagatt 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga agcagagacc actttatttt 180 gtgcatcaga tgctaaagca tataacacag aggcacataa tgtgtgggcc acacatgcct 240 gtgtaccaac agaccctagc ccacaagaag tattattggt aaatgtgaca gaaaattata 300 acatgtggaa aaataacatg gtagaacaga tgcatgagga tataattagt ttatgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cgctttgtgt tactttaaat tgcactaatg 420 tgaattgcac tcatgagaat ggtaccacta ccgagtgcgg taataatggg atacagatgg 480 agaaaggaga aatgaaaaac tgctctttca atattaccac aagcataaaa aataagatgc 540 agaaagaata tgcacttttg tataaactag atttagcatc aataggtaat gataatacaa 600 gctatacttt gataagttgt aacacctcag tcattacaca ggcctgtcca aagatatcct 660 ttgaaccaat tccaatacat tattgtgccc cggctggttt tgcgattcta aaatgtaatg 720 ataagaactt caagggaaca ggatcatgta aaaatgtcag cacagtacaa tgtacacatg 780 gaattaagcc agtagtgtca actcaattgt tgttaaatgg cactttagca gaaacagagg 840 tagtaattag atctgaaaat atcacagaca atgctaaaac cataatagta caactgaagg 900 accctgtaaa aattaattgt acaagacctg gcaacaatac agcaagaagc atacatatgg 960 gaccggggag agcattttct gcaacaggac aaataatagg aaatataaga caagcacatt 1020 gtaaccttag tagaacagaa tgggatgaca ctttaaaaaa gatagctaag aaattaggag 1080 aacaatttag gaataaaagt atagccttta atcaatcctc aggaggggac ccagaaattg 1140 taatgcacag ttttaattgt ggaggggaat ttttttactg taatacatca cagctgttta 1200 atagtacttg gtggaacaat ggtactagga atgatgctgc aaggtcaaat agcactgaac 1260 ctatcacact ccggtgcagt ataaagcaaa ttataaacag atggcaggaa gtaggaaaag 1320 caatgtatgc ccctcccatc aggggaaacg ttacatgtaa ctcaagtatt acagggctac 1380 tcttaataag agatggtggg aacagtaatg agtctactga gaccttcaga cctcagggag 1440 gaaatatgaa ggacaattgg agaagtgaat tatacaaata taaagtagta aaaattgagc 1500 cattaggagt agcacccacc aaggcaaaga gaagagtggt gcagagagaa aaaagagcag 1560 tgggactagg agctgtgttc cttgggttct tgggagcagc aggaagcact 1610 <210> 124 <211> 484 <212> PRT <213> Human immunodeficiency virus type 1 <400> 124 Ser Ala Glu Glu Asp Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Glu Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asn Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Ser Pro Gln Glu Val Leu Leu Val Asn Val Thr Glu Asn     50 55 60 Tyr Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asn Val Asn Cys Thr His Glu Asn             100 105 110 Gly Thr Thr Thr Glu Cys Gly Asn Asn Gly Ile Gln Met Glu Lys Gly         115 120 125 Glu Met Lys Asn Cys Ser Phe Asn Ile Thr Thr Ser Ile Lys Asn Lys     130 135 140 Met Gln Lys Glu Tyr Ala Leu Leu Tyr Lys Leu Asp Leu Ala Ser Ile 145 150 155 160 Gly Asn Asp Asn Thr Ser Tyr Thr Leu Ile Ser Cys Asn Thr Ser Val                 165 170 175 Ile Thr Gln Ala Cys Pro Lys Ile Ser Phe Glu Pro Ile Pro Ile His             180 185 190 Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys Asn         195 200 205 Phe Lys Gly Thr Gly Ser Cys Lys Asn Val Ser Thr Val Gln Cys Thr     210 215 220 His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Thr 225 230 235 240 Leu Ala Glu Thr Glu Val Val Ile Arg Ser Glu Asn Ile Thr Asp Asn                 245 250 255 Ala Lys Thr Ile Ile Val Gln Leu Lys Asp Pro Val Lys Ile Asn Cys             260 265 270 Thr Arg Pro Gly Asn Asn Thr Ala Arg Ser Ile His Met Gly Pro Gly         275 280 285 Arg Ala Phe Ser Ala Thr Gly Gln Ile Ile Gly Asn Ile Arg Gln Ala     290 295 300 His Cys Asn Leu Ser Arg Thr Glu Trp Asp Asp Thr Leu Lys Lys Ile 305 310 315 320 Ala Lys Lys Leu Gly Glu Gln Phe Arg Asn Lys Ser Ile Ala Phe Asn                 325 330 335 Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys             340 345 350 Gly Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gln Leu Phe Asn Ser Thr         355 360 365 Trp Trp Asn Asn Gly Thr Arg Asn Asp Ala Ala Arg Ser Asn Ser Thr     370 375 380 Glu Pro Ile Thr Leu Arg Cys Ser Ile Lys Gln Ile Ile Asn Arg Trp 385 390 395 400 Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Asn Val                 405 410 415 Thr Cys Asn Ser Ser Ile Thr Gly Leu Leu Leu Ile Arg Asp Gly Gly             420 425 430 Asn Ser Asn Glu Ser Thr Glu Thr Phe Arg Pro Gln Gly Gly Asn Met         435 440 445 Lys Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile     450 455 460 Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln 465 470 475 480 Arg Glu Lys Arg                  <210> 125 <211> 1619 <212> DNA <213> Human immunodeficiency virus type 1 <400> 125 agaaagagca gaagacagtg gcaatgagag tgatggggat aaagaagaat tactggtgga 60 gatggggccc gatgctcctt gggatattga tgacctatag tgcagcagaa ttttgggtca 120 cagtctacta tggagtgcca gtgtggaaag aaacaaccac cactctattt tgtgcatcag 180 atgccaaagc atatgataca gaggcacata atgtttgggc cacacatgcc tgtgtaccca 240 cagaccccaa cccacaagaa gtagtattgg aaaaggtgac agaagagttt aacatgtgga 300 aaaatagcat ggtagaacag atgcatgagg atataatcag tttatgggat caaagtctaa 360 agccatgtgt aaaactaacc ccactctgtg ttactttaag ttgcactgat tgtaatggta 420 ctagccctga gtgtgcgaag aatgctagta ctactaccac tagtagtaag ggattgatag 480 ataaagggga aataaaaaac tgctctttca atgccaccac acacataatg gataaggtgc 540 agaaagaata tgcattattt tataacactg atttagtaca aatagagggt gagaaatctg 600 ataataatac tagatatagg ttaataagtt gtaacacctc agtcattaaa caggcctgtc 660 caaaggtatc ttttgagcca attcccatac attattgtgc cccggctggt tttgcgattc 720 taaagtgtaa agataagaat ttcaatggaa caggaaaatg ttacaatgtc agcacagtac 780 aatgtacaca tggaattagg ccagtaatgt caactcaact gctgttaaat ggcagcctag 840 cagaagaaga aatagtaatt agatctgcca atttctcgaa caatgctaaa accataatag 900 tacatctgaa tgaatctgta gaaattaact gcacaagacc caacaacgat acaaggaaaa 960 gtataaatat aggaccaggg agagcatggt atgcagcagg agaaataata ggaaatataa 1020 gaaaagcata ttgtaacatt agcagagcaa aatggaacaa cactttaaaa catgtagttg 1080 aaaaactaag aaaacaattt ggaaataaaa caataaactt tacacaacac gcaggagggg 1140 acctagaaat tgtgacgcat agttttaatt gtggagggga attcttctac tgcaacacaa 1200 cacagctgtt taatagtact tggcctaaga atggtacttg gaatggtact ggtagtgaca 1260 ttatcacact cccatgcaaa ataaaacaga ttataaacat gtggcaggag gtaggaaaag 1320 caatgtatgc ccctcccatc agcggactaa ttagatgttc atcaaatatt acagggctgc 1380 tattaacaag agatggtggt aagggtaatg gcacaaatga tacagagatc ttcagaccag 1440 gaggaggaga tatgagggac aattggagaa gtgaattata taaatataaa gtagtagaaa 1500 ttgagccaat aggactagca cccaccaagg caaagagaag agtggtgcag agagaaaaaa 1560 gagcagtggg aacgctggga gctatgttcc ttgggttctt gggagcagca ggaagcact 1619 <210> 126 <211> 488 <212> PRT <213> Human immunodeficiency virus type 1 <400> 126 Ser Ala Ala Glu Phe Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp 1 5 10 15 Lys Glu Thr Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr             20 25 30 Asp Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr         35 40 45 Asp Pro Asn Pro Gln Glu Val Val Leu Glu Lys Val Thr Glu Glu Phe     50 55 60 Asn Met Trp Lys Asn Ser Met Val Glu Gln Met His Glu Asp Ile Ile 65 70 75 80 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu                 85 90 95 Cys Val Thr Leu Ser Cys Thr Asp Cys Asn Gly Thr Ser Pro Glu Cys             100 105 110 Ala Lys Asn Ala Ser Thr Thr Thr Thr Ser Ser Lys Gly Leu Ile Asp         115 120 125 Lys Gly Glu Ile Lys Asn Cys Ser Phe Asn Ala Thr Thr His Ile Met     130 135 140 Asp Lys Val Gln Lys Glu Tyr Ala Leu Phe Tyr Asn Thr Asp Leu Val 145 150 155 160 Gln Ile Glu Gly Glu Lys Ser Asp Asn Asn Thr Arg Tyr Arg Leu Ile                 165 170 175 Ser Cys Asn Thr Ser Val Ile Lys Gln Ala Cys Pro Lys Val Ser Phe             180 185 190 Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu         195 200 205 Lys Cys Lys Asp Lys Asn Phe Asn Gly Thr Gly Lys Cys Tyr Asn Val     210 215 220 Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Met Ser Thr Gln 225 230 235 240 Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Ile Val Ile Arg Ser                 245 250 255 Ala Asn Phe Ser Asn Asn Ala Lys Thr Ile Ile Val His Leu Asn Glu             260 265 270 Ser Val Glu Ile Asn Cys Thr Arg Pro Asn Asn Asp Thr Arg Lys Ser         275 280 285 Ile Asn Ile Gly Pro Gly Arg Ala Trp Tyr Ala Ala Gly Glu Ile Ile     290 295 300 Gly Asn Ile Arg Lys Ala Tyr Cys Asn Ile Ser Arg Ala Lys Trp Asn 305 310 315 320 Asn Thr Leu Lys His Val Val Glu Lys Leu Arg Lys Gln Phe Gly Asn                 325 330 335 Lys Thr Ile Asn Phe Thr Gln His Ala Gly Gly Asp Leu Glu Ile Val             340 345 350 Thr His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Thr         355 360 365 Gln Leu Phe Asn Ser Thr Trp Pro Lys Asn Gly Thr Trp Asn Gly Thr     370 375 380 Gly Ser Asp Ile Ile Thr Leu Pro Cys Lys Ile Lys Gln Ile Ile Asn 385 390 395 400 Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser Gly                 405 410 415 Leu Ile Arg Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp             420 425 430 Gly Gly Lys Gly Asn Gly Thr Asn Asp Thr Glu Ile Phe Arg Pro Gly         435 440 445 Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys     450 455 460 Val Val Glu Ile Glu Pro Ile Gly Leu Ala Pro Thr Lys Ala Lys Arg 465 470 475 480 Arg Val Val Gln Arg Glu Lys Arg                 485 <210> 127 <211> 1613 <212> DNA <213> Human immunodeficiency virus type 1 <400> 127 agaaagagca gaagacagtg gcaatgagag cgaaggggat caggaagagt tgtcaacact 60 tatggagatg gggcaccatg ctccttggga tgttgatgat ttgtagtgct gcagaaaact 120 tgtgggtcac agtctactat ggggtacctg tgtggaaaga agcaaccacc actctatttt 180 gtgcatcgaa tgctaaagca tatgagacag aggtgcataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaag tagtattggg aaatgtgaca gaaaatttta 300 acatgtggaa aaataacatg gtagaacaga tgcatgagga tgtaattagt ttgtgggacc 360 aaagcttaaa gccatgtgta aaattgaccc cactctgtgt tactttacat tgcactgatt 420 gtgagaatac tattactggg gggaataata ctaatagtaa atgcaatgag gataagggga 480 atactactgc cactatattg atagagaaag gagagatgaa aaactgctct tttaatgtca 540 ccacagacct aagagataag atgcagaaag aatatgcact tgatgtagta ccattagaca 600 gtactaatac cagctataag ttagtaagtt gtaacacctc agtcattaca caggcctgtc 660 caaaggtatc ttttgagcca attccaatac atttctgtgc cccagctggt tttgcgattc 720 taaagtgtaa caataaaacg tttgatggaa aaggaccatg tacaaatgtc agtacagtgc 780 gatgtacaca tggaattaaa ccagtagtgt caactcaact gctgttaaat ggcagtctag 840 cagaagaaga gatagtgatt agatctgaaa atttctcgaa caatgctaaa accataatag 900 tacagctaaa taaaactgta gaaattaatt gtacaagacc caacaacaac acaagcaaag 960 gtatacatat gggaccaggg agggcatttt atgcaacagg aagaatagta ggagatataa 1020 gacaagcaca ttgtaacatt agtaacgcag attggacaaa tactttaaaa caggtagcta 1080 ggaaattaag ggaacaatat gtgaataaaa caatagcctt taagccaccc tcaggagggg 1140 acccagaagt tgtactgcac acttttaatt gtagagggga atttttctac tgtaatttat 1200 caagaatgtt taatagtagt tttaattcaa cacaactgtc taattattca gaagatactg 1260 ggaccatcac agtcccatgc agaataaaac aatttataaa catgtggcag gaagtaggaa 1320 aagcaatgta tgcccctccc atcagaggag aaattaattg ttcatcaaag attacaggat 1380 tgttattaac aagagacggt ggcaatagca atgggactga gattttcaga cctggaggag 1440 gagatatgag ggacaattgg agaagtgaat tatacaaata taaagtagta agaattgaac 1500 cattaggatt agcacccacc aaggcaaaga gaagagtggt gcagagagaa aaaagagcag 1560 cagtgacaat gggagcaatg ttccctgggt tcttgggagc agcaggaagc act 1613 <210> 128 <211> 484 <212> PRT <213> Human immunodeficiency virus type 1 <400> 128 Ser Ala Ala Glu Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asn Ala Lys Ala             20 25 30 Tyr Glu Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Gly Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Val 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu His Cys Thr Asp Cys Glu Asn Thr Ile Thr Gly             100 105 110 Gly Asn Asn Thr Asn Ser Lys Cys Asn Glu Asp Lys Gly Asn Thr Thr         115 120 125 Ala Thr Ile Leu Ile Glu Lys Gly Glu Met Lys Asn Cys Ser Phe Asn     130 135 140 Val Thr Thr Asp Leu Arg Asp Lys Met Gln Lys Glu Tyr Ala Leu Asp 145 150 155 160 Val Val Pro Leu Asp Ser Thr Asn Thr Ser Tyr Lys Leu Val Ser Cys                 165 170 175 Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro             180 185 190 Ile Pro Ile His Phe Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys         195 200 205 Asn Asn Lys Thr Phe Asp Gly Lys Gly Pro Cys Thr Asn Val Ser Thr     210 215 220 Val Arg Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu 225 230 235 240 Leu Asn Gly Ser Leu Ala Glu Glu Glu Ile Val Ile Arg Ser Glu Asn                 245 250 255 Phe Ser Asn Asn Ala Lys Thr Ile Ile Val Gln Leu Asn Lys Thr Val             260 265 270 Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Ser Lys Gly Ile His         275 280 285 Met Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly Arg Ile Val Gly Asp     290 295 300 Ile Arg Gln Ala His Cys Asn Ile Ser Asn Ala Asp Trp Thr Asn Thr 305 310 315 320 Leu Lys Gln Val Ala Arg Lys Leu Arg Glu Gln Tyr Val Asn Lys Thr                 325 330 335 Ile Ala Phe Lys Pro Pro Ser Gly Gly Asp Pro Glu Val Val Leu His             340 345 350 Thr Phe Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Leu Ser Arg Met         355 360 365 Phe Asn Ser Ser Phe Asn Ser Thr Gln Leu Ser Asn Tyr Ser Glu Asp     370 375 380 Thr Gly Thr Ile Thr Val Pro Cys Arg Ile Lys Gln Phe Ile Asn Met 385 390 395 400 Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Glu                 405 410 415 Ile Asn Cys Ser Ser Lys Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly             420 425 430 Gly Asn Ser Asn Gly Thr Glu Ile Phe Arg Pro Gly Gly Gly Asp Met         435 440 445 Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile     450 455 460 Glu Pro Leu Gly Leu Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln 465 470 475 480 Arg Glu Lys Arg                  <210> 129 <211> 1640 <212> DNA <213> Human immunodeficiency virus type 1 <400> 129 agaaagagca gaagacagtg gcaatgagag tgaaggggat caggaagaat tatcagcact 60 tatggagatg gggcaccgtg ctccttggga tgttgatgat ctgtagtgct gtagaacaat 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga agcaaccacc actttatttt 180 gtgcatcaga tgctaaagca tatgacacag aggcacataa tgtctgggcc acacatgcct 240 gtgtacctac agaccctaac ccacaagaag tagtattgga aaatgtgaca gaagattcta 300 acatgtggaa aaataacatg gtagaacaga tgcatgagga tataatcagt ttatgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cactctgtgt tactctaaat tgcactgatt 420 tcaattgtac tagttccagc aatactacta atagcacttg cattggtacc catcggacta 480 ctaataccga tggtagggag aaattggaaa tggaggtagg agaaataaaa aactgctctt 540 tcaatgtcac cacaagcata aggaataagg tacagaaaga atatgcactt ttttataaac 600 ttgatgtaat gccaatagat agtacgagct atacattgat acattgcaac acttcaacca 660 ttacacaggc ctgtccaaag gtatcctttg aaccaattcc tatacattat tgtgccccgg 720 ctggttttgc gattctaaag tgtaacaata agacgttcag tggaaaagga ccatgtaaaa 780 atgtcagcac agttcaatgt acacatggaa ttaggccagt agtgtcaact caactgctgt 840 taaatggtag tctagcagaa gaagagatag taattaggtc tgacaatttc tcggacaatg 900 ctaaaatcat aatagtacac ctaaataaat ctatagaaat taattgtaca agacccaaca 960 ataatacaag aaaaagaata tcgatggggc cgggaagagt atattataca acaggacaaa 1020 taataggaga tataagaaaa gcacattgta atattagtgg agaagaatgg aatagaacgt 1080 taaaagggat agttataaaa ttaagagaac aatttgggaa gaataaaaca atcatctttg 1140 atagatcctc aggaggggac ctagaaattg aaatgcatag ttttaattgt ggaggagagt 1200 tcttctactg taatacaaca aaactattta atagtgcttg gaatgagtca ggttacaatg 1260 ggacaaattc taatggaact attacactcc catgcagaat aagacaaatt gtaaacaggt 1320 ggcaggaagt aggaaaagca atgtatgccc ctcccatcac aggacaaatt aggtgttcat 1380 caaatattac aggactaata ttaacaagag atggtggtaa cagtagcaat agtagtaatg 1440 tgaatgagac cttcagacct acaggaggag atatgaggga caattggaga agtgaattat 1500 ataaatataa agtaatacga attgagccaa taggagtagc acccaccaag gcaaagagaa 1560 gagtggtgca gagagagaaa agagcagtgg gaacgctagg agctatgttc cttgggttct 1620 tgggagcagc aggaagcact 1640 <210> 130 <211> 493 <212> PRT <213> Human immunodeficiency virus type 1 <400> 130 Ser Ala Val Glu Gln Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Glu Asn Val Thr Glu Asp     50 55 60 Ser Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Phe Asn Cys Thr Ser Ser Ser             100 105 110 Asn Thr Thr Asn Ser Thr Cys Ile Gly Thr His Arg Thr Thr Asn Thr         115 120 125 Asp Gly Arg Glu Lys Leu Glu Met Glu Val Gly Glu Ile Lys Asn Cys     130 135 140 Ser Phe Asn Val Thr Thr Ser Ile Arg Asn Lys Val Gln Lys Glu Tyr 145 150 155 160 Ala Leu Phe Tyr Lys Leu Asp Val Met Pro Ile Asp Ser Thr Ser Tyr                 165 170 175 Thr Leu Ile His Cys Asn Thr Ser Thr Ile Thr Gln Ala Cys Pro Lys             180 185 190 Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe         195 200 205 Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Ser Gly Lys Gly Pro Cys     210 215 220 Lys Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val 225 230 235 240 Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Ile Val                 245 250 255 Ile Arg Ser Asp Asn Phe Ser Asp Asn Ala Lys Ile Ile Ile Val His             260 265 270 Leu Asn Lys Ser Ile Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr         275 280 285 Arg Lys Arg Ile Ser Met Gly Pro Gly Arg Val Tyr Tyr Thr Thr Gly     290 295 300 Gln Ile Ile Gly Asp Ile Arg Lys Ala His Cys Asn Ile Ser Gly Glu 305 310 315 320 Glu Trp Asn Arg Thr Leu Lys Gly Ile Val Ile Lys Leu Arg Glu Gln                 325 330 335 Phe Gly Lys Asn Lys Thr Ile Ile Phe Asp Arg Ser Ser Gly Gly Asp             340 345 350 Leu Glu Ile Glu Met His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr         355 360 365 Cys Asn Thr Thr Lys Leu Phe Asn Ser Ala Trp Asn Glu Ser Gly Tyr     370 375 380 Asn Gly Thr Asn Ser Asn Gly Thr Ile Thr Leu Pro Cys Arg Ile Arg 385 390 395 400 Gln Ile Val Asn Arg Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro                 405 410 415 Pro Ile Thr Gly Gln Ile Arg Cys Ser Ser Asn Ile Thr Gly Leu Ile             420 425 430 Leu Thr Arg Asp Gly Gly Asn Ser Ser Asn Ser Ser Asn Val Asn Glu         435 440 445 Thr Phe Arg Pro Thr Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu     450 455 460 Leu Tyr Lys Tyr Lys Val Ile Arg Ile Glu Pro Ile Gly Val Ala Pro 465 470 475 480 Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg                 485 490 <210> 131 <211> 1664 <212> DNA <213> Human immunodeficiency virus type 1 <400> 131 agaaagagca gaagacagtg gcaatgaaag cgaaggagat gaagaagcat tggcagcact 60 tgtggaaagg gggcatcatg ctccttggga tgttaatgat ctgtagtgct gcaccaaact 120 tgtgggtcac agtctattat ggggtacctg tgtggaaaga agcaaccacc actctatttt 180 gtgcatcaga tgctaaagca tacaaaacag aggctcataa tgtctgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaag tagtattgga aaatgtgaca gaaaatttta 300 acatgtggaa aaataacatg gtagaacaga tgcatgagga tataattagt ctatgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cactctgtgt tactttaaat tgcactaagt 420 taaataattg cactgagttg cagaatgata ctacgaatag tactacgttg gagaatggta 480 cttattgcat taaggtggag aataaaacta atataaggga agaaatgaca aattgctctt 540 tcaatattac cacaagtgta agagataagg tgcataaaca atatgctctc ttctatagat 600 ttgatttagt accaatagag gatgaaaata agaatactag ctctaataat agctttagat 660 tgataaattg taatacctca atcattacac agtcctgtcc aaaggtaacc tttgagccaa 720 ttcccataca ttattgtacc ccagctggtt ttgcgattct aaagtgtaat gataagaagt 780 tcaatggaaa agggccatgt acaaatgtca gcacagtaca atgtacacat ggaattaaac 840 cagtagtgtc aactcaactg ctgttaaatg gcagtctagc agaagaagag gtagtaatta 900 gatctgaaaa cttcacaaac aatgctaaaa ccataatagt acagctgaac gagactgtag 960 aaattaattg tacaagacct agcaacaata caagaaaaag tataactata ggaccaggga 1020 gagcattttt tacaacaggg gatgtaatag gaaatataag gcaagcatat tgtaacgtta 1080 gtagggcaaa atggaataac actttaagac agatagttac aaaactaaga gaacaatttg 1140 agaataaaac aataattttt aagtcatcct cgggagggga cccagaaatt gtaactcaca 1200 cttttaattg tggaggagaa tttttctact gtaatacaac accactgttt aatagtacct 1260 gggataatag tacctgggat tggaataata ctgaagagtc aaacagcact cccattgtac 1320 tcacatgcag aataaaacaa attgtaaata tgtggcagga ggtaggaaaa gcaatgtatg 1380 cccctcccat cagaggacaa atttggtgtt catcaaatat tacaggactg ctattaacaa 1440 gagatggtgg aataaataat acgggaaatg agaccttcag acctgcagga ggagatatga 1500 gggacaattg gagaagtgaa tcatataaat ataaagtagt aagaattgaa ccattaggag 1560 tggcacccac caaggcaaag agaagagtgg tgcagagaga aaaaagagca gtgggaacaa 1620 taggagctat gttccttggg ttcttgggag cagcaggaag cact 1664 <210> 132 <211> 501 <212> PRT <213> Human immunodeficiency virus type 1 <400> 132 Ser Ala Ala Pro Asn Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Lys Thr Glu Ala His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Glu Asn Val Thr Glu Asn     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Lys Leu Asn Asn Cys Thr Glu Leu             100 105 110 Gln Asn Asp Thr Thr Asn Ser Thr Thr Leu Glu Asn Gly Thr Tyr Cys         115 120 125 Ile Lys Val Glu Asn Lys Thr Asn Ile Arg Glu Glu Met Thr Asn Cys     130 135 140 Ser Phe Asn Ile Thr Thr Ser Val Arg Asp Lys Val His Lys Gln Tyr 145 150 155 160 Ala Leu Phe Tyr Arg Phe Asp Leu Val Pro Ile Glu Asp Glu Asn Lys                 165 170 175 Asn Thr Ser Ser Asn Asn Ser Phe Arg Leu Ile Asn Cys Asn Thr Ser             180 185 190 Ile Ile Thr Gln Ser Cys Pro Lys Val Thr Phe Glu Pro Ile Pro Ile         195 200 205 His Tyr Cys Thr Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys     210 215 220 Lys Phe Asn Gly Lys Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys 225 230 235 240 Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly                 245 250 255 Ser Leu Ala Glu Glu Glu Val Val Ile Arg Ser Glu Asn Phe Thr Asn             260 265 270 Asn Ala Lys Thr Ile Ile Val Gln Leu Asn Glu Thr Val Glu Ile Asn         275 280 285 Cys Thr Arg Pro Ser Asn Asn Thr Arg Lys Ser Ile Thr Ile Gly Pro     290 295 300 Gly Arg Ala Phe Phe Thr Thr Gly Asp Val Ile Gly Asn Ile Arg Gln 305 310 315 320 Ala Tyr Cys Asn Val Ser Arg Ala Lys Trp Asn Asn Thr Leu Arg Gln                 325 330 335 Ile Val Thr Lys Leu Arg Glu Gln Phe Glu Asn Lys Thr Ile Ile Phe             340 345 350 Lys Ser Ser Ser Gly Gly Asp Pro Glu Ile Val Thr His Thr Phe Asn         355 360 365 Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr Thr Pro Leu Phe Asn Ser     370 375 380 Thr Trp Asp Asn Ser Thr Trp Asp Trp Asn Asn Thr Glu Glu Ser Asn 385 390 395 400 Ser Thr Pro Ile Val Leu Thr Cys Arg Ile Lys Gln Ile Val Asn Met                 405 410 415 Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Gln             420 425 430 Ile Trp Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly         435 440 445 Gly Ile Asn Asn Thr Gly Asn Glu Thr Phe Arg Pro Ala Gly Gly Asp     450 455 460 Met Arg Asp Asn Trp Arg Ser Glu Ser Tyr Lys Tyr Lys Val Val Arg 465 470 475 480 Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val                 485 490 495 Gln Arg Glu Lys Arg             500 <210> 133 <211> 1640 <212> DNA <213> Human immunodeficiency virus type 1 <133> 133 agaaagagca gaagacagtg gcaatgaaag cgaaggagac caggaagaac tatcagcgct 60 tgtggagatg gggcacgatg ctccttggga tgttgatgat ctgtagtgct acagaaaaat 120 tgtgggtcac agtctactat ggggtacctg tgtggaaaga agcaactacc actctatttt 180 gtgcatcaga tgctaaagca tatgatacgg aggtacataa tgtttgggcc acacatgcct 240 gtgtacccac agaccccaac ccacaagaag tagtattggt aaatgtaaca gaaaagttta 300 acatgtggaa aaataacatg gtagaacaaa tgcatgagga cataatcaat ctatgggatc 360 aaagcctaaa gccatgtgta aaattaaccc cgctctgtat tactttaaat tgctctgatg 420 ttagaaattg cactgagcag gggaatgata ctgccgctag tacttgtatt gattggaaga 480 ctaatggtag tgagaaagtg atggagaaag gagaaataaa aaactgctct ttcaatatta 540 caacaaacat aagggacaag gtgaaggaag agtatgcact tttttataaa attgatatag 600 caccaataga taatgatact actagctata ggttgataaa ttgtaacacc tcagtcatta 660 cacaggcctg tccaaaggta tcctttgagc caattcccat acattattgt gccccggctg 720 gttttgcgat tctaaaatgt ggagataaga agttcaatgg aacaggacta tgtaaaaatg 780 tcagcacagt acaatgtaca catggaatta ggccagtagt gtcaactcaa ctgctgttaa 840 acggcagtct agcagaagaa gatgtaataa ttagatctgc caatttcaca gacaatgcta 900 aaaacataat agtacagctg aaggaatctg tagaaattac ttgtataaga cccaacaata 960 caagaaaaag tattcatata ggaccaggga aaacattttt tacaacagaa ataataggaa 1020 atataagaca agcatattgt acccttgatg gaacaaaatg gaataacact ttagcacaga 1080 tagttgaaca attaagggga caatttggaa ataaaacaat agactttaag caaccctcag 1140 gaggggaccc agaagttata atgcacaagt ttaattgtgg aggggaattt ttctactgta 1200 attcaacaca actgtttaat agtacttggc cactaaatgg tactagatca ggtggcactg 1260 aaggaagcac tgaaggaaat atcacactcc catgtaaaat aaaacaaatt ataaacaggt 1320 ggcaggaagt aggaaaagca atgtatgccc ctcccatcaa aggaataatt agatgttcat 1380 cgaatattac agggctgata ttaacaagag atggtgggga gggcaagaac gataccaaca 1440 gtaccgagat cttcagacct ggaggaggag atatgaggga caattggaga agtgaattat 1500 ataaatataa agtagtacga attgaaccat taggagtagc acccaccaag gcaaagagaa 1560 gagtggtgca gagagaaaaa agagcagtgg ggatgctagg agctatgttc cttgggttct 1620 tgggagcagc aggaagcact 1640 <210> 134 <211> 493 <212> PRT <213> Human immunodeficiency virus type 1 <400> 134 Ser Ala Thr Glu Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Lys Glu Ala Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Val Asn Val Thr Glu Lys     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Asn Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Ile Thr Leu Asn Cys Ser Asp Val Arg Asn Cys Thr Glu Gln             100 105 110 Gly Asn Asp Thr Ala Ala Ser Thr Cys Ile Asp Trp Lys Thr Asn Gly         115 120 125 Ser Glu Lys Val Met Glu Lys Gly Glu Ile Lys Asn Cys Ser Phe Asn     130 135 140 Ile Thr Thr Asn Ile Arg Asp Lys Val Lys Glu Glu Tyr Ala Leu Phe 145 150 155 160 Tyr Lys Ile Asp Ile Ala Pro Ile Asp Asn Asp Thr Thr Ser Tyr Arg                 165 170 175 Leu Ile Asn Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val             180 185 190 Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala         195 200 205 Ile Leu Lys Cys Gly Asp Lys Lys Phe Asn Gly Thr Gly Leu Cys Lys     210 215 220 Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser 225 230 235 240 Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Asp Val Ile Ile                 245 250 255 Arg Ser Ala Asn Phe Thr Asp Asn Ala Lys Asn Ile Val Gln Leu             260 265 270 Lys Glu Ser Val Glu Ile Thr Cys Ile Arg Pro Asn Asn Thr Arg Lys         275 280 285 Ser Ile His Ile Gly Pro Gly Lys Thr Phe Phe Thr Thr Glu Ile Ile     290 295 300 Gly Asn Ile Arg Gln Ala Tyr Cys Thr Leu Asp Gly Thr Lys Trp Asn 305 310 315 320 Asn Thr Leu Ala Gln Ile Val Glu Gln Leu Arg Gly Gln Phe Gly Asn                 325 330 335 Lys Thr Ile Asp Phe Lys Gln Pro Ser Gly Gly Asp Pro Glu Val Ile             340 345 350 Met His Lys Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr         355 360 365 Gln Leu Phe Asn Ser Thr Trp Pro Leu Asn Gly Thr Arg Ser Gly Gly     370 375 380 Thr Glu Gly Ser Thr Glu Gly Asn Ile Thr Leu Pro Cys Lys Ile Lys 385 390 395 400 Gln Ile Ile Asn Arg Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro                 405 410 415 Pro Ile Lys Gly Ile Ile Arg Cys Ser Ser Asn Ile Thr Gly Leu Ile             420 425 430 Leu Thr Arg Asp Gly Gly Glu Gly Lys Asn Asp Thr Asn Ser Thr Glu         435 440 445 Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu     450 455 460 Leu Tyr Lys Tyr Lys Val Val Arg Ile Glu Pro Leu Gly Val Ala Pro 465 470 475 480 Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg                 485 490 <210> 135 <211> 1672 <212> DNA <213> Human immunodeficiency virus type 1 <400> 135 agaagagcag aagacagtgg caatgaaagt gaaggagacc aggaagaatt atcagaactt 60 atggagatgg ggcatcttgc tccttgggat attaatgatc tgtagtgctg cagaaaaatt 120 gtgggtaaca gtctattatg gggtacctgt gtggagagaa gcaaacacca ctttattttg 180 tgcatcagat gctaaagcat atgatacaga agtacataat gtctgggcca cacatgcctg 240 tgtgcccaca gaccccaacc cacaagaagt agtattggga aatgtgacag aatattttaa 300 tatgtggaaa aataacatgg tagaacagat gcatgaggat ataatcagtt tatgggatca 360 aagcctaaag ccatgtgtaa aattaactcc actctgtgtt actttaaatt gcactgatgc 420 agtctgtact tcaaattgca ctaattccac tggtacgtcc actcctattc ccaccactgt 480 tagcagtgag gacaaaggag aaataaaaaa ctgctctttc aatgtcacca caagcataaa 540 agataggata cagagagaat atgcaacttt ttataagctt gatgtagtac caatagatga 600 tgatgataat actagagatg ataataatac tagtaataat aatactagta accctagtaa 660 gactctctat aggttgataa attgtaacac ctcagccctt acacaggcct gtccaaaggt 720 atcctttgaa ccaattccca tacattattg tgccccagct ggttttgcga ttctaaagtg 780 taacaataag acattcgatg gatcgggacc atgtacaaat gtcagcacag tacaatgtac 840 acatggaatt aggccagtag tgtcaactca attgctgtta aatggcagtc tagcagaagg 900 agatatagta atcagatctg aaaatttctc gaacaatgct aaaaccataa tagtacagct 960 gaaggaatct ataagcatta attgtacaag acccaacaac aatacaagaa aaagtataca 1020 tataggacaa ggaagggcat tttatacaac aggagatata ataggagata taagaaaagc 1080 acattgtaac gttagtagag aaggttggaa taacgctgta aaccgactag ttgaaaaatt 1140 aaaagaacaa tttggaaaaa gaaaaacaat aaaatttaag ccatcctcag gaggggaccc 1200 agagattgta atgcacatgt ttaattgtgg aggggagttt ttctactgta atacatcaaa 1260 actgtttaat gttgttaatg atacttggat gggatcaaat gacactggag aaatcgagct 1320 cccatgtaga ataaaacaaa tcgtaagcat gtggcaggaa gtaggaaaag caatgtatgc 1380 ccctcccatc agaggacaaa ttagatgttc atcagatatc acagggctgc tattaacaag 1440 agatggtggt aaggatgaca acaacacaat tggaaatgaa accttcagac ctggaggagg 1500 agatatgagg gacaattgga gaagtgaatt atataaatat aaagtagtaa aaattcaacc 1560 actaggaata gcacccacca aggcaaagag aagagtggtg cagagagaaa aaagagcagt 1620 gggagcacta ggagctatgt tccttgggtt cttgggagca gcaggaagca ct 1672 <210> 136 <211> 504 <212> PRT <213> Human immunodeficiency virus type 1 <400> 136 Ser Ala Ala Glu Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val 1 5 10 15 Trp Arg Glu Ala Asn Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala             20 25 30 Tyr Asp Thr Glu Val His Asn Val Trp Ala Thr His Ala Cys Val Pro         35 40 45 Thr Asp Pro Asn Pro Gln Glu Val Val Leu Gly Asn Val Thr Glu Tyr     50 55 60 Phe Asn Met Trp Lys Asn Asn Met Val Glu Gln Met His Glu Asp Ile 65 70 75 80 Ile Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro                 85 90 95 Leu Cys Val Thr Leu Asn Cys Thr Asp Ala Val Cys Thr Ser Asn Cys             100 105 110 Thr Asn Ser Thr Gly Thr Ser Thr Pro Ile Pro Thr Thr Val Ser Ser         115 120 125 Glu Asp Lys Gly Glu Ile Lys Asn Cys Ser Phe Asn Val Thr Thr Ser     130 135 140 Ile Lys Asp Arg Ile Gln Arg Glu Tyr Ala Thr Phe Tyr Lys Leu Asp 145 150 155 160 Val Val Pro Ile Asp Asp Asp Asp Asn Thr Arg Asp Asp Asn Asn Thr                 165 170 175 Ser Asn Asn Asn Thr Ser Asn Pro Ser Lys Thr Leu Tyr Arg Leu Ile             180 185 190 Asn Cys Asn Thr Ser Ala Leu Thr Gln Ala Cys Pro Lys Val Ser Phe         195 200 205 Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu     210 215 220 Lys Cys Asn Asn Lys Thr Phe Asp Gly Ser Gly Pro Cys Thr Asn Val 225 230 235 240 Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser Thr Gln                 245 250 255 Leu Leu Leu Asn Gly Ser Leu Ala Glu Gly Asp Ile Val Ile Arg Ser             260 265 270 Glu Asn Phe Ser Asn Asn Ala Lys Thr Ile Ile Val Gln Leu Lys Glu         275 280 285 Ser Ile Ser Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser     290 295 300 Ile His Ile Gly Gln Gly Arg Ala Phe Tyr Thr Thr Gly Asp Ile Ile 305 310 315 320 Gly Asp Ile Arg Lys Ala His Cys Asn Val Ser Arg Glu Gly Trp Asn                 325 330 335 Asn Ala Val Asn Arg Leu Val Glu Lys Leu Lys Glu Gln Phe Gly Lys             340 345 350 Arg Lys Thr Ile Lys Phe Lys Pro Ser Ser Gly Gly Asp Pro Glu Ile         355 360 365 Val Met His Met Phe Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Thr     370 375 380 Ser Lys Leu Phe Asn Val Val Asn Asp Thr Trp Met Gly Ser Asn Asp 385 390 395 400 Thr Gly Glu Ile Glu Leu Pro Cys Arg Ile Lys Gln Ile Val Ser Met                 405 410 415 Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Arg Gly Gln             420 425 430 Ile Arg Cys Ser Ser Asp Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly         435 440 445 Gly Lys Asp Asp Asn Asn Thr Ile Gly Asn Glu Thr Phe Arg Pro Gly     450 455 460 Gly Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys 465 470 475 480 Val Val Lys Ile Gln Pro Leu Gly Ile Ala Pro Thr Lys Ala Lys Arg                 485 490 495 Arg Val Val Gln Arg Glu Lys Arg             500 <210> 137 <211> 1533 <212> DNA <213> Human immunodeficiency virus type 1 <400> 137 atgagagtga aggagaaata tcagcacttg tggagatggg ggtggagatg gggcaccatg 60 ctccttggga tgttgatgat ctgtagtgct acagaaaaat tgtgggtcac agtctattat 120 ggggtacctg tgtggaagga agcaaccacc actctatttt gtgcatcaga tgctaaagca 180 tatgatacag aggtacataa tgtttgggcc acacatgcct gtgtacccac agaccccaac 240 ccacaagaag tagtattggt aaatgtgaca gaaaatttta acatgtggaa aaatgacatg 300 gtagaacaga tgcatgagga tataatcagt ttatgggatc aaagcctaaa gccatgtgta 360 aaattaaccc cactctgtgt tagtttaaag tgcactgatt tgaagaatga tactaatacc 420 aatagtagta gcgggagaat gataatggag aaaggagaga taaaaaactg ctctttcaat 480 atcagcacaa gcataagagg taaggtgcag aaagaatatg cattttttta taaacttgat 540 ataataccaa tagataatga tactaccagc tataagttga caagttgtaa cacctcagtc 600 attacacagg cctgtccaaa ggtatccttt gagccaattc ccatacatta ttgtgccccg 660 gctggttttg cgattctaaa atgtaataat aagacgttca atggaacagg accatgtaca 720 aatgtcagca cagtacaatg tacacatgga attaggccag tagtatcaac tcaactgctg 780 ttaaatggca gtctagcaga agaagaggta gtaattagat ctgtcaattt cacggacaat 840 gctaaaacca taatagtaca gctgaacaca tctgtagaaa ttaattgtac aagacccaac 900 aacaatacaa gaaaaagaat ccgtatccag agaggaccag ggagagcatt tgttacaata 960 ggaaaaatag gaaatatgag acaagcacat tgtaacatta gtagagcaaa atggaataac 1020 actttaaaac agatagctag caaattaaga gaacaatttg gaaataataa aacaataatc 1080 tttaagcaat cctcaggagg ggacccagaa attgtaacgc acagttttaa ttgtggaggg 1140 gaatttttct actgtaattc aacacaactg tttaatagta cttggtttaa tagtacttgg 1200 agtactgaag ggtcaaataa cactgaagga agtgacacaa tcaccctccc atgcagaata 1260 aaacaaatta taaacatgtg gcagaaagta ggaaaagcaa tgtatgcccc tcccatcagt 1320 ggacaaatta gatgttcatc aaatattaca gggctgctat taacaagaga tggtggtaat 1380 agcaacaatg agtccgagat cttcagacct ggaggaggag atatgaggga caattggaga 1440 agtgaattat ataaatataa agtagtaaaa attgaaccat taggagtagc acccaccaag 1500 gcaaagagaa gagtggtgca gagagaaaaa aga 1533 <210> 138 <211> 511 <212> PRT <213> Human immunodeficiency virus type 1 <400> 138 Met Arg Val Lys Glu Lys Tyr Gln His Leu Trp Arg Trp Gly Trp Arg 1 5 10 15 Trp Gly Thr Met Leu Leu Gly Met Leu Met Ile Cys Ser Ala Thr Glu             20 25 30 Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala         35 40 45 Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu     50 55 60 Val His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn 65 70 75 80 Pro Gln Glu Val Val Leu Val Asn Val Thr Glu Asn Phe Asn Met Trp                 85 90 95 Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp             100 105 110 Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Ser         115 120 125 Leu Lys Cys Thr Asp Leu Lys Asn Asp Thr Asn Thr Asn Ser Ser Ser     130 135 140 Gly Arg Met Ile Met Glu Lys Gly Glu Ile Lys Asn Cys Ser Phe Asn 145 150 155 160 Ile Ser Thr Ser Ile Arg Gly Lys Val Gln Lys Glu Tyr Ala Phe Phe                 165 170 175 Tyr Lys Leu Asp Ile Ile Pro Ile Asp Asn Asp Thr Thr Ser Tyr Lys             180 185 190 Leu Thr Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val         195 200 205 Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala     210 215 220 Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys Thr 225 230 235 240 Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser                 245 250 255 Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile             260 265 270 Arg Ser Val Asn Phe Thr Asp Asn Ala Lys Thr Ile Ile Val Gln Leu         275 280 285 Asn Thr Ser Val Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg     290 295 300 Lys Arg Ile Arg Ile Gln Arg Gly Pro Gly Arg Ala Phe Val Thr Ile 305 310 315 320 Gly Lys Ile Gly Asn Met Arg Gln Ala His Cys Asn Ile Ser Arg Ala                 325 330 335 Lys Trp Asn Asn Thr Leu Lys Gln Ile Ala Ser Lys Leu Arg Glu Gln             340 345 350 Phe Gly Asn Asn Lys Thr Ile Ile Phe Lys Gln Ser Ser Gly Gly Asp         355 360 365 Pro Glu Ile Val Thr His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr     370 375 380 Cys Asn Ser Thr Gln Leu Phe Asn Ser Thr Trp Phe Asn Ser Thr Trp 385 390 395 400 Ser Thr Glu Gly Ser Asn Asn Thr Glu Gly Ser Asp Thr Ile Thr Leu                 405 410 415 Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Lys Val Gly Lys             420 425 430 Ala Met Tyr Ala Pro Pro Ile Ser Gly Gln Ile Arg Cys Ser Ser Asn         435 440 445 Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Ser Asn Asn Glu     450 455 460 Ser Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg 465 470 475 480 Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val                 485 490 495 Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg             500 505 510 <139> <211> 511 <212> PRT <213> Artificial <220> <223> HIV-1 HXB2 gp120 with Cys mutations of U-101c1 <400> 139 Met Arg Val Lys Glu Lys Tyr Gln His Leu Trp Arg Trp Gly Trp Arg 1 5 10 15 Trp Gly Thr Met Leu Leu Gly Met Leu Met Ile Cys Ser Ala Thr Glu             20 25 30 Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala         35 40 45 Thr Thr Thr Leu Phe Arg Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu     50 55 60 Val His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn 65 70 75 80 Pro Gln Glu Val Val Leu Val Asn Val Thr Glu Asn Phe Asn Met Trp                 85 90 95 Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp             100 105 110 Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Arg Val Ser         115 120 125 Leu Lys Cys Thr Asp Leu Lys Asn Asp Thr Asn Thr Asn Ser Ser Ser     130 135 140 Gly Arg Met Ile Met Glu Lys Gly Glu Ile Lys Asn Cys Ser Phe Asn 145 150 155 160 Ile Ser Thr Ser Ile Arg Gly Lys Val Gln Lys Glu Tyr Ala Phe Phe                 165 170 175 Tyr Lys Leu Asp Ile Ile Pro Ile Asp Asn Asp Thr Thr Ser Tyr Lys             180 185 190 Leu Thr Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val         195 200 205 Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala     210 215 220 Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys Thr 225 230 235 240 Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser                 245 250 255 Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile             260 265 270 Arg Ser Val Asn Phe Thr Asp Asn Ala Lys Thr Ile Ile Val Gln Leu         275 280 285 Asn Thr Ser Val Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg     290 295 300 Lys Arg Ile Arg Ile Gln Arg Gly Pro Gly Arg Ala Phe Val Thr Ile 305 310 315 320 Gly Lys Ile Gly Asn Met Arg Gln Ala His Cys Asn Ile Ser Arg Ala                 325 330 335 Lys Trp Asn Asn Thr Leu Lys Gln Ile Ala Ser Lys Leu Arg Glu Gln             340 345 350 Phe Gly Asn Asn Lys Thr Ile Ile Phe Lys Gln Ser Ser Gly Gly Asp         355 360 365 Pro Glu Ile Val Thr His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr     370 375 380 Cys Asn Ser Thr Gln Leu Phe Asn Ser Thr Trp Phe Asn Ser Thr Trp 385 390 395 400 Ser Thr Glu Gly Ser Asn Asn Thr Glu Gly Ser Asp Thr Ile Thr Leu                 405 410 415 Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Lys Val Gly Lys             420 425 430 Ala Met Tyr Ala Pro Pro Ile Ser Gly Gln Ile Arg Cys Ser Ser Asn         435 440 445 Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Ser Asn Asn Glu     450 455 460 Ser Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg 465 470 475 480 Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val                 485 490 495 Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg             500 505 510 <210> 140 <211> 511 <212> PRT <213> Artificial <220> <223> HIV-1 HXB2 gp120 with Cys mutations of U-178c13 <400> 140 Met Arg Val Lys Glu Lys Tyr Gln His Leu Trp Arg Trp Gly Trp Arg 1 5 10 15 Trp Gly Thr Met Leu Leu Gly Met Leu Met Ile Cys Ser Ala Thr Glu             20 25 30 Lys Leu Trp Val Thr Val Tyr Tyr Gly Val Pro Val Trp Lys Glu Ala         35 40 45 Thr Thr Thr Leu Phe Cys Ala Ser Asp Ala Lys Ala Tyr Asp Thr Glu     50 55 60 Val His Asn Val Trp Ala Thr His Ala Cys Val Pro Thr Asp Pro Asn 65 70 75 80 Pro Gln Glu Val Val Leu Val Asn Val Thr Glu Asn Phe Asn Met Trp                 85 90 95 Lys Asn Asp Met Val Glu Gln Met His Glu Asp Ile Ile Ser Leu Trp             100 105 110 Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu Cys Val Ser         115 120 125 Leu Lys Arg Thr Asp Leu Lys Asn Asp Thr Asn Thr Asn Ser Ser Ser     130 135 140 Gly Arg Met Ile Met Glu Lys Gly Glu Ile Lys Asn Cys Ser Phe Asn 145 150 155 160 Ile Ser Thr Ser Ile Arg Gly Lys Val Gln Lys Glu Tyr Ala Phe Phe                 165 170 175 Tyr Lys Leu Asp Ile Ile Pro Ile Asp Asn Asp Thr Thr Ser Tyr Lys             180 185 190 Leu Thr Ser Cys Asn Thr Ser Val Ile Thr Gln Ala Cys Pro Lys Val         195 200 205 Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Phe Ala     210 215 220 Ile Leu Lys Tyr Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys Thr 225 230 235 240 Asn Val Ser Thr Val Gln Cys Thr His Gly Ile Arg Pro Val Val Ser                 245 250 255 Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Glu Glu Val Val Ile             260 265 270 Arg Ser Val Asn Phe Thr Asp Asn Ala Lys Thr Ile Ile Val Gln Leu         275 280 285 Asn Thr Ser Val Glu Ile Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg     290 295 300 Lys Arg Ile Arg Ile Gln Arg Gly Pro Gly Arg Ala Phe Val Thr Ile 305 310 315 320 Gly Lys Ile Gly Asn Met Arg Gln Ala His Cys Asn Ile Ser Arg Ala                 325 330 335 Lys Trp Asn Asn Thr Leu Lys Gln Ile Ala Ser Lys Leu Arg Glu Gln             340 345 350 Phe Gly Asn Asn Lys Thr Ile Ile Phe Lys Gln Ser Ser Gly Gly Asp         355 360 365 Pro Glu Ile Val Thr His Ser Phe Asn Cys Gly Gly Glu Phe Phe Tyr     370 375 380 Cys Asn Ser Thr Gln Leu Phe Asn Ser Thr Trp Phe Asn Ser Thr Trp 385 390 395 400 Ser Thr Glu Gly Ser Asn Asn Thr Glu Gly Ser Asp Thr Ile Thr Leu                 405 410 415 Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Lys Val Gly Lys             420 425 430 Ala Met Tyr Ala Pro Pro Ile Ser Gly Gln Ile Arg Cys Ser Ser Asn         435 440 445 Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Asn Ser Asn Asn Glu     450 455 460 Ser Glu Ile Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg 465 470 475 480 Ser Glu Leu Tyr Lys Tyr Lys Val Val Lys Ile Glu Pro Leu Gly Val                 485 490 495 Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys Arg             500 505 510

Claims (63)

(a) an immunogenic composition comprising an isolated polypeptide comprising a first gp120 amino acid sequence or an isolated polynucleotide encoding such a first gp120 amino acid sequence and a pharmaceutically acceptable carrier, wherein the first gp120 sequence comprises At least V2, V3 and C4 domains, (i) the first gp120 sequence is 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, 331, Lack one or more cysteine residues at one or more of positions 378, 385, 418, and 445, (ii) the first gp120 sequence is 24, 29, 34, 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, One or more additional cysteines at positions other than 247, 296, 331, 378, 385, 418, 445, 493, 495, 499 to 501, 503 to 508 and 510 Contains residues, The position is numbered from the N-terminal methionine of gp120 from the HXB-2 strain of HIV gp120, An immunogenic composition wherein the first gp120 sequence is not a subtype G gp120 sequence with one or more additional cysteines in the V1 domain or a subtype E gp120 sequence with one or more additional cysteines in the V4 domain. The immunogenic composition of claim 1, wherein the first gp120 sequence further comprises a V1 domain. The immunogenic composition of claim 1, wherein the immunogenic composition further comprises an adjuvant. The immunogenic composition of claim 1, wherein the first gp120 sequence comprises a native gp120 sequence. The immunogenic composition of claim 4, wherein the first gp120 sequence comprises a gp120 sequence from a primary isolate of HIV. The immunogenic composition of claim 1 comprising a polypeptide comprising a first gp120 sequence. The immunogenic composition of claim 1 comprising a polynucleotide encoding a first gp120 sequence. The method of claim 1, wherein the first gp120 sequence is 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, An immunogenic composition characterized by the lack of one or more cysteine residues at one or more of positions 331, 378, 385, 418 and 445. The method of claim 8, wherein the first gp120 sequence is 54, 74, 119, 126, 157, 205, 218, 228, 239, 247, 331, 378 or 385. An immunogenic composition characterized by the lack of one or more cysteine residues in one or more positions. The method of claim 1, wherein the first gp120 sequence is 24, 29, 34, 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, One or more positions other than 239, 247, 296, 331, 378, 385, 418, 445, 493, 495, 499 to 501, 503 to 508 and 510 An immunogenic composition comprising additional cysteine residues. The method of claim 10, wherein the first gp120 sequence is 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, Immunization comprising one or more additional cysteine residues at positions other than 331, 378, 385, 418 or 445, provided that at least one additional cysteine residue is not present in the V1 domain of gp120 Original composition. The immunogenic composition of claim 1, wherein the first gp120 sequence comprises an odd number of cysteines. The immunogenic composition of claim 12, wherein the composition comprises a polypeptide comprising a first gp120 sequence and the cysteine in the first gp120 sequence is covalently linked with another polypeptide. The immunogenic composition of claim 13, wherein the covalent bond comprises a disulfide bond. The immunogenic composition of claim 13, wherein the other polypeptide comprises a second gp120 sequence. The immunogenic composition of claim 15, wherein the second gp120 sequence is identical to the first gp120 sequence and these gp120 sequences form a homodimer. The immunogenic composition of claim 15, wherein the second gp120 sequence is different from the first gp120 sequence and these gp120 sequences form a heterodimer. The immunogenic composition of claim 13, wherein the other polypeptide comprises a gp41 amino acid sequence. The composition of claim 12, wherein the composition comprises a polypeptide comprising a first gp120 sequence, wherein the cysteine in the gp120 sequence is selected from the group consisting of a cell-specific binding moiety, a drug, an immunostimulatory oligonucleotide, and an immunogenic carrier protein. An immunogenic composition, characterized in that it is covalently bonded. The immunogenic composition of claim 1, wherein the polypeptide comprises a fusion polypeptide comprising a first gp120 sequence, or wherein the polynucleotide encodes such a fusion polypeptide. The method of claim 1, wherein the first gp120 sequence is SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36 , 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86 , 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134 and 136 An immunogenic composition characterized by having at least about 99% identity with each of the V1, V2, V3, and C4 domains of gp120 selected from the group consisting of: The method of claim 21, wherein the first gp120 sequence is SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36 , 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86 , 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134 and 136 An immunogenic composition comprising at least the V1, V2, V3 and C4 domains of gp120 selected from the group consisting of: An isolated polypeptide comprising a first gp120 amino acid sequence, wherein the first gp120 sequence comprises at least the V2, V3, and C4 domains of gp120, (a) the first gp120 sequence is at least one of positions 54, 74, 119, 126, 157, 205, 218, 228, 239, 247, 331, 378 or 385 Lack one or more cysteine residues in (b) the first gp120 sequence is 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, 331, At least one additional cysteine residue at one or more of positions 378, 385, 418, or 445, This position is numbered from the N-terminal methionine of gp120 from the HXB-2 strain of HIV gp120, An isolated polypeptide wherein the first gp120 sequence is not a subtype E gp120 sequence with one or more additional cysteines in the V4 domain. The polypeptide of claim 23, wherein the first gp120 sequence further comprises a V1 domain. The method of claim 23, wherein the first gp120 sequence is 54, 74, 119, 126, 157, 205, 218, 228, 239, 247, 331, 378 or 385 A polypeptide characterized by the lack of one or more cysteine residues in one or more positions. The method of claim 23, wherein the first gp120 sequence is 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, A polypeptide comprising at least one additional cysteine residue at a position other than 331, 378, 385, 418 or 445, provided that at least one additional cysteine residue is not present in the V1 domain of gp120 . The polypeptide of claim 23, wherein the first gp120 sequence comprises an odd number of cysteines. The polypeptide of claim 27, wherein the cysteine in the gp120 sequence is covalently linked with another polypeptide. The polypeptide of claim 28, wherein the covalent bond is a disulfide bond. The polypeptide of claim 28, wherein the other polypeptide comprises a second gp120 sequence. 31. The polypeptide of claim 30, wherein the second gp120 sequence is identical to the first gp120 sequence and these gp120 sequences form a homodimer. 31. The polypeptide of claim 30, wherein the second gp120 sequence is different from the first gp120 sequence and these gp120 sequences form a heterodimer. The polypeptide of claim 28, wherein the other polypeptide comprises a gp41 amino acid sequence. The polypeptide of claim 27, wherein the cysteine in the gp120 sequence is covalently linked to an agent selected from the group consisting of cell-specific binding moieties, drugs, immunostimulatory oligonucleotides and immunogenic carrier proteins. The polypeptide of claim 23, wherein the polypeptide comprises a fusion polypeptide comprising a first gp120 sequence. 36. The polypeptide of claim 35, wherein the fusion polypeptide comprises a heterologous signal sequence. The polypeptide of claim 36, wherein the heterologous signal sequence is selected from the herpes simplex virus glycoprotein D (gD-1) signal sequence and the human tissue plasminogen activator signal sequence. 37. The polypeptide of claim 35 or 36, wherein the polypeptide comprises an epitope tag. SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, V1, V2, of gp120 selected from the group consisting of 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134 and 136; An isolated polypeptide comprising a first gp120 amino acid sequence having at least about 99% identity with each of the V3 and C4 domains. The method of claim 39, wherein the first gp120 sequence is SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36 , 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86 , 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134 and 136 A polypeptide comprising at least the V1, V2, V3 and C4 domains of gp120 selected from the group consisting of: 41. An isolated polynucleotide encoding a polypeptide of any one of claims 23-27 and 35-40. 42. The polynucleotide of claim 41, wherein the polynucleotide is codon optimized for expression in a host cell of a particular species. The method of claim 41, wherein the polynucleotide is SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 , 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88 , 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134 and 136 A polynucleotide, characterized by encoding a gp120 amino acid sequence having at least about 99% identity with each of the V1, V2, V3, and C4 domains of gp120 selected from the group. The method of claim 43, wherein the polynucleotide is SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 , 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87 , 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135 or these And a gp120 nucleotide sequence selected from the group consisting of subsequences of, wherein the subsequence encodes at least the V1, V2, V3, and C4 domains of gp120. A vector comprising the polynucleotide of claim 41. 46. The vector of claim 45, wherein the vector comprises an expression vector. 46. The vector of claim 45, wherein the vector comprises a viral vector. A host cell comprising the vector of claim 45. 49. The host cell of claim 48, wherein the host cell is selected from mammalian cells and bacterial cells. (a) introducing the vector of claim 45 into a cell, (b) producing a polypeptide comprising the first gp120 amino acid sequence, including expressing the polypeptide. 51. The method of claim 50, wherein the cell is in vivo. 51. The method of claim 50, wherein the cells are in culture. 53. The method of claim 52, further comprising recovering the polypeptide from the culture. (a) the host cell of claim 48 comprising the expression vector is cultured under conditions suitable for expression of the polypeptide, (b) A method for producing a polypeptide comprising the first gp120 amino acid sequence, comprising recovering the polypeptide from the culture. A method of immunizing an animal with a polypeptide comprising the first gp120 sequence, comprising administering the immunogenic composition of claim 1 to the animal. (a) contacting a biological sample from a subject with an isolated polypeptide comprising a gp120 amino acid sequence, wherein the gp120 sequence comprises at least the V2, V3, and C4 domains of gp120, (i) The gp120 sequences are 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, 331 and 378. Lack one or more cysteine residues at one or more of positions 385, 418 and 445, and / or (ii) gp120 sequence is 24, 29, 34, 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247 One or more additional cysteine residues at positions other than 296, 331, 378, 385, 418, 445, 493, 495, 499-501, 503-508 and 510. Including, This position is numbered from the N-terminal methionine of gp120 from the HXB-2 strain of HIV gp120, the gp120 sequence is not a subtype G gp120 sequence with one or more additional cysteines in the V1 domain or a subtype E gp120 sequence with one or more additional cysteines in the V4 domain; And (b) determining whether the biological sample comprises an antibody that specifically binds to the isolated polypeptide. The method of claim 56, wherein the gp120 sequence further comprises a V1 domain. Biological samples from the subject were numbered from the N-terminal methionine of gp120 from the HXB-2 strain of HIV gp120 (a) 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247, 296, 331, 378, 385 Lack one or more cysteine residues at one or more of positions 418 and 445, and / or (b) 24, 29, 34, 54, 74, 119, 126, 131, 157, 196, 205, 218, 228, 239, 247 and 296 Gp120 comprising one or more additional cysteine residues at positions other than 331, 378, 385, 418, 445, 493, 495, 499 to 501, 503 to 508 and 510 A method of diagnosis comprising assaying a biological sample from a subject to determine whether it comprises a polypeptide comprising an amino acid sequence or a polynucleotide encoding such a gp120 amino acid sequence. 59. The method of claim 58, wherein the gp120 sequence is not a subtype G gp120 sequence with one or more additional cysteines in the V1 domain or a subtype E gp120 sequence with one or more additional cysteines in the V4 domain. 59. The method of claim 58, wherein the assay comprises contacting the sample with an antibody that specifically binds to the gp120 sequence under conditions suitable for binding. 59. The method of claim 58, wherein the assay comprises contacting the sample polynucleotide with a nucleic acid molecule that is hybridized specifically to the nucleotide sequence encoding the gp120 sequence under conditions suitable for hybridization. 62. The method of claim 61, wherein the nucleic acid molecule is one of a pair of amplification primers, and wherein the assay comprises contacting the sample polynucleotide with both amplification primers under conditions suitable for amplification, wherein the crystal produced an amplification product. Diagnostic method comprising determining whether or not. 62. The method of claim 61, wherein the nucleic acid molecule is a nucleic acid probe attached to a solid phase.

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